Acts as the sensor component of the NLRP1 inflammasome, which mediates inflammasome activation in response to various pathogen-associated signals, leading to subsequent pyroptosis (PubMed:22665479, PubMed:12191486, PubMed:17349957, PubMed:27662089, PubMed:31484767, PubMed:33093214, PubMed:33731929, PubMed:33731932). Inflammasomes are supramolecular complexes that assemble in the cytosol in response to pathogens and other damage-associated signals and play critical roles in innate immunity and inflammation (PubMed:22665479, PubMed:12191486, PubMed:17349957). Acts as a recognition receptor (PRR): recognizes specific pathogens and other damage-associated signals, such as cleavage by human rhinoviruses 14 and 16 (HRV-14 and HRV-16), double-stranded RNA or Val-boroPro inhibitor, and mediates the formation of the inflammasome polymeric complex composed of NLRP1, CASP1 and PYCARD/ASC (PubMed:22665479, PubMed:12191486, PubMed:17349957, PubMed:30291141, PubMed:33243852, PubMed:33093214). In response to pathogen-associated signals, the N-terminal part of NLRP1 is degraded by the proteasome, releasing the cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-containing protein 1, C-terminus), which polymerizes and associates with PYCARD/ASC to initiate the formation of the inflammasome complex: the NLRP1 inflammasome recruits pro-caspase-1 (proCASP1) and promotes caspase-1 (CASP1) activation, which subsequently cleaves and activates inflammatory cytokines IL1B and IL18 and gasdermin-D (GSDMD), leading to pyroptosis (PubMed:22665479, PubMed:12191486, PubMed:17349957, PubMed:32051255, PubMed:33093214). Activation of NLRP1 inflammasome is also required for HMGB1 secretion; the active cytokines and HMGB1 stimulate inflammatory responses (PubMed:22801494). Binds ATP and shows ATPase activity (PubMed:11113115, PubMed:15212762, PubMed:33243852). Plays an important role in antiviral immunity and inflammation in the human airway epithelium (PubMed:33093214). Specifically recognizes a number of pathogen-associated signals: upon infection by human rhinoviruses 14 and 16 (HRV-14 and HRV-16), NLRP1 is cleaved and activated which triggers NLRP1-dependent inflammasome activation and IL18 secretion (PubMed:33093214). Positive-strand RNA viruses such as. Semliki forest virus and long dsRNA activate the NLRP1 inflammasome, triggering IL1B release in a NLRP1-dependent fashion (PubMed:33243852). Acts as a direct sensor for long dsRNA and thus RNA virus infection (PubMed:33243852). May also be activated by muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, in a NOD2-dependent manner (PubMed:18511561). Constitutes the precursor of the NLRP1 inflammasome, which mediates autoproteolytic processing within the FIIND domain to generate the N-terminal and C-terminal parts, which are associated non-covalently in absence of pathogens and other damage-associated signals. Regulatory part that prevents formation of the NLRP1 inflammasome: in absence of pathogens and other damage-associated signals, interacts with the C-terminal part of NLRP1 (NACHT, LRR and PYD domains-containing protein 1, C-terminus), preventing activation of the NLRP1 inflammasome (PubMed:33093214). In response to pathogen-associated signals, this part is ubiquitinated and degraded by the proteasome, releasing the cleaved C-terminal part of the protein, which polymerizes and forms the NLRP1 inflammasome (PubMed:33093214). Constitutes the active part of the NLRP1 inflammasome (PubMed:33093214, PubMed:33731929, PubMed:33731932). In absence of pathogens and other damage-associated signals, interacts with the N-terminal part of NLRP1 (NACHT, LRR and PYD domains-containing protein 1, N-terminus), preventing activation of the NLRP1 inflammasome (PubMed:33093214). In response to pathogen-associated signals, the N-terminal part of NLRP1 is degraded by the proteasome, releasing this form, which polymerizes and associates with PYCARD/ASC to form of the NLRP1 inflammasome complex: the NLRP1 inflammasome complex then directly recruits pro-caspase-1 (proCASP1) and promotes caspase-1 (CASP1) activation, leading to gasdermin-D (GSDMD) cleavage and subsequent pyroptosis (PubMed:33093214). It is unclear whether is involved in inflammasome formation. It is not cleaved within the FIIND domain, does not assemble into specks, nor promote IL1B release (PubMed:22665479). However, in an vitro cell-free system, it has been shown to be activated by MDP (PubMed:17349957). ATP + H2O = ADP + H(+) + phosphate NLRP1 inflammasome is activated by cleavage by human rhinoviruses 14 and 16 (HRV-14 and HRV-16): cleavage promotes ubiquitination and degradation of the N-terminal part, releasing the cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-containing protein 1, C-terminus), which polymerizes and forms the NLRP1 inflammasome (PubMed:33093214). Activated double-stranded RNA: positive-strand RNA viruses such as Semliki forest virus and long dsRNA activate the NLRP1 inflammasome (PubMed:33243852). In contrast to its mouse ortholog, not activated by Bacillus anthracis lethal toxin (PubMed:19651869). NLRP1 inflammasome is inhibited by DPP8 and DPP9, which sequester the C-terminal fragment of NLRP1 (NACHT, LRR and PYD domains-containing protein 1, C-terminus) in a ternary complex, thereby preventing NLRP1 oligomerization and activation (PubMed:30291141, PubMed:31525884, PubMed:33731929, PubMed:33731932). NLRP1 inflammasome is activated by Val-boroPro (Talabostat, PT-100), an inhibitor of dipeptidyl peptidases DPP8 and DPP9 (PubMed:30291141, PubMed:33731929, PubMed:33731932). Val-boroPro relieves inhibition of DPP8 and/or DPP9 by promoting disruption of the ternary complex, releasing its C-terminal part from autoinhibition (PubMed:33731929, PubMed:33731932). ATPase activity is activated by dsRNA-binding but not dsDNA-binding (PubMed:33243852). Interacts (via LRR repeats) with BCL2 and BCL2L1 (via the loop between motifs BH4 and BH3); these interactions reduce NLRP1 inflammasome-induced CASP1 activation and IL1B release, possibly by impairing NLRP1 interaction with PYCARD (PubMed:17418785). Interacts with NOD2; this interaction is enhanced in the presence of muramyl dipeptide (MDP) and increases IL1B release (PubMed:18511561). Interacts with EIF2AK2/PKR; this interaction requires EIF2AK2 activity, is accompanied by EIF2AK2 autophosphorylation and promotes inflammasome assembly in response to danger-associated signals (PubMed:22801494). Interacts with MEFV; this interaction targets NLRP1 to degradation by autophagy, hence preventing excessive IL1B- and IL18-mediated inflammation (PubMed:17431422, PubMed:26347139). Binds (via LRR domain) to dsDNA and dsRNA (PubMed:33243852). Interacts with DPP9; leading to inhibit activation of the inflammasome (PubMed:30291141, PubMed:31525884, PubMed:33731932). DPP9 acts via formation of a ternary complex, composed of a DPP9 homodimer, one full-length NLRP1 protein, and one cleaved C-terminus of NLRP1 (NACHT, LRR and PYD domains-containing protein 1, C-terminus) (PubMed:33731932). Interacts with DPP8; leading to inhibit activation of the inflammasome, probably via formation of a ternary complex with DPP8 (PubMed:31525884). Interacts with the C-terminal part of NLRP1 (NACHT, LRR and PYD domains-containing protein 1, C-terminus) in absence of pathogens and other damage-associated signals. Interacts with the N-terminal part of NLRP1 (NACHT, LRR and PYD domains-containing protein 1, N-terminus) in absence of pathogens and other damage-associated signals (PubMed:33093214). Homomultimer; forms the NLRP1 inflammasome polymeric complex, a filament composed of homopolymers of this form in response to pathogens and other damage-associated signals (PubMed:33420028, PubMed:33420033). The NLRP1 inflammasome polymeric complex associates with PYCARD/ASC (PubMed:22665479, PubMed:12191486, PubMed:17418785, PubMed:17349957). Interacts (via CARD domain) with PYCARD/ASC (via CARD domain); leading to pro-caspase-1 (proCASP1) recruitment (PubMed:22665479, PubMed:12191486, PubMed:17418785). Pro-caspase-1 (proCASP1) filament formation increases local enzyme concentration, resulting in trans-autocleavage and activation (PubMed:22665479, PubMed:12191486, PubMed:17349957). Active CASP1 then processes IL1B and IL18 precursors, leading to the release of mature cytokines in the extracellular milieu and inflammatory response (PubMed:22665479, PubMed:12191486, PubMed:17349957). (Microbial infection) Interacts with vaccinia virus protein F1 (PubMed:16439990). Nucleocytoplasmic distribution in lymphoid organs (probably in T-cells) and in neurons. In epithelial cells, predominantly cytoplasmic. Widely expressed (PubMed:11113115, PubMed:17164409). Abundantly expressed in primary immune cells (isoform 1 and isoform 2), including in neutrophils, monocytes/macrophages, dendritic cells (mostly Langerhans cells), and B- and T-lymphocytes (at protein level) (PubMed:15285719, PubMed:17164409). Strongly expressed in epithelial cells lining the glandular epithelium, such as that of the gastrointestinal tract (stomach, small intestine, colon), the respiratory tract (trachea and bronchi), and the endometrial and endocervical glands, gallbladder, prostate, and breast (at protein level). In testis, expressed in spermatogonia and primary spermatocytes, but not in Sertoli cells (at protein level). In the brain, expressed in neurons, in particular in pyramidal ones and in oligodendrocytes, but not detected in microglia (at protein level) (PubMed:17164409). Expressed in adult and fetal ocular tissues, including in adult and 24-week old fetal choroid, sclera, cornea, and optic nerve, as well as in adult retina and fetal retina/retinal pigment epithelium (PubMed:23349227). Highly expressed in the skin throughout the epidermis and in dermal fibroblasts, in both glabrous skin and plantar skin. It is detected in keratinocytes, but not in melanocytes. Expressed in epidermal appendages such as hair follicles (PubMed:27662089). Associated with differentiation in stratified epithelia of the skin, esophagus, intestine, and cervix, as well as in the prostate gland. Undetectable in undifferentiated basal cells, but expressed in differentiated luminal secretory cells (PubMed:11113115). Expressed in differentiated macrophages and granulocytes, but not their precursors (at protein level) (PubMed:11113115, PubMed:15285719). In testis, also associated with cell differentiation, with conflicting results. Expressed in spermatogonia and primary spermatocytes, but not in cells from later differentiation stages, including secondary spermatocytes, spermatids, and spermatozoa (at protein level) (PubMed:17164409). Not detected in spermatocytes, nor spermatids, and strongly expressed in spermatozoa (at protein level) (PubMed:11113115). Up-regulated by ATF4 during endoplasmic reticulum (ER) stress response (PubMed:26086088). Up-regulated in arterial endothelial cells exposed to plasma from patients with peripheral arterial disease, but not to plasma from healthy controls (PubMed:24439873). The CARD domain, rather than the pyrin domain, is involved in the interaction with PYCARD, CASP1 and CASP5. The leucine-rich repeat (LRR) domain may be involved in autoinhibition in the absence of activating signal, possibly through intramolecular interaction with the NACHT domain. Serves as the predominant binding domain for dsRNA and dsDNA (PubMed:33243852). The FIIND (domain with function to find) region is involved in homomerization, but not in CASP1-binding (By similarity). Autocatalytic cleavage in this region occurs constitutively, prior to activation signals, and is required for inflammasome activity (IL1B release), possibly by facilitating CASP1 binding (PubMed:22665479, PubMed:22087307). Both N- and C-terminal fragments remain associated (PubMed:22665479, PubMed:22087307). The pyrin domain mediates an autoinhibitory function, potentially acting as a threshold modulator, which allows NLRP1 to discriminate long from short dsRNA. Inhibits ATPase activity of the NATCH domain. The C-terminal part of NLRP1 oligomerizes to form the core of the NLRP1 inflammasome filament: in the filament, the CARD domains form a central helical filaments that are promoted by oligomerized, but flexibly linked, UPA regions surrounding the filaments (PubMed:33420028, PubMed:33420033). The UPA region reduces the threshold needed for filament formation and signaling (PubMed:33420028, PubMed:33420033). Must recruit the adapter PYCARD/ASC to facilitate CASP1 interaction and polymerization (PubMed:33420033). Upon dsRNA-binding via its LRR domain, NACHT domain gains ATPase activity which is inhibited by the pyrin domain. Autocatalytically cleaved (PubMed:22087307, PubMed:22665479, PubMed:33093214). Autocatalytic cleavage in FIIND region occurs constitutively, prior to activation signals, and is required for inflammasome activity (IL1B release), possibly by facilitating CASP1 binding (PubMed:22087307, PubMed:22665479, PubMed:33093214). Both N- and C-terminal parts remain associated non-covalently (PubMed:22087307, PubMed:22665479, PubMed:33093214). Ubiquitinated by the cullin:ZER1/ZYG11B complex in response to pathogen-associated signals, leading to its degradation by the proteasome and subsequent release of the cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-containing protein 1, C-terminus), which polymerizes and forms the NLRP1 inflammasome. (Microbial infection) Cleaved between Gln-130 and Gly-131 by human rhinovirus 14 (HRV-14) Protease 3C. This cleavage triggers N-glycine-mediated proteasomal degradation of the autoinhibitory NLRP1 N-terminal fragment via the cullin:ZER1/ZYG11B complex which liberates the activating C-terminal fragment and activates NLRP1 inflammasome. Disease susceptibility is associated with variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease may be caused by variants affecting the gene represented in this entry. The disease may be caused by variants affecting the gene represented in this entry. In macrophages and dendritic cells, NLRP1 inflammasome activation of CASP1 and IL1B maturation can be dampened by direct contact with activated effector and memory T-cells. This effect may be mediated by hexameric TNF ligands, such as CD40LG. Belongs to the NLRP family. Extended N-terminus.