Acts as the sensor component of the Nlrp1b inflammasome, which mediates inflammasome activation in response to various pathogen-associated signals, leading to subsequent pyroptosis (By similarity). 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 (By similarity). Acts as a recognition receptor (PRR): recognizes specific pathogens and other damage-associated signals, such as B.anthracis lethal toxin (LT) or Val-boroPro inhibitor, and mediates the formation of the inflammasome polymeric complex (PubMed:16429160, PubMed:31383852). In response to pathogen-associated signals, the N-terminal part of Nlrp1b is degraded by the proteasome, releasing the cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-containing protein 1b, C-terminus), which polymerizes to initiate the formation of the inflammasome complex: the inflammasome directly recruits pro-caspase-1 (proCASP1) independently of PYCARD/ASC and promotes caspase-1 (CASP1) activation, which subsequently cleaves and activates inflammatory cytokines IL1B and IL18 and gasdermin-D (GSDMD), leading to pyroptosis (By similarity). Activation of Nlrp1b inflammasome is also required for HMGB1 secretion; the active cytokines and HMGB1 stimulate inflammatory responses (By similarity). Primary mediator of macrophage susceptibility to B.anthracis LT: in response to B.anthracis infection, macrophages and dendritic cells release IL1B and undergo pyroptosis (PubMed:16429160, PubMed:24935976). This early inflammatory response to the toxin increases resistance to infection by B.anthracis spores (PubMed:16429160, PubMed:24935976). Constitutes the precursor of the Nlrp1b 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 Nlrp1b inflammasome: in absence of pathogens and other damage-associated signals, interacts with the C-terminal part of Nlrp1b (NACHT, LRR and PYD domains-containing protein 1b, C-terminus), preventing activation of the Nlrp1b inflammasome. In response to pathogen-associated signals, this part is ubiquitinated by the N-end rule pathway and degraded by the proteasome, releasing the cleaved C-terminal part of the protein, which polymerizes and forms the Nlrp1b inflammasome. Constitutes the active part of the Nlrp1b inflammasome. In absence of pathogens and other damage-associated signals, interacts with the N-terminal part of Nlrp1b (NACHT, LRR and PYD domains-containing protein 1b, N-terminus), preventing activation of the Nlrp1b inflammasome. In response to pathogen-associated signals, the N-terminal part of Nlrp1b is degraded by the proteasome, releasing this form, which polymerizes to form the Nlrp1b inflammasome complex: the Nlrp1b inflammasome complex then directly recruits pro-caspase-1 (proCASP1) and promotes caspase-1 (CASP1) activation, leading to gasdermin-D (GSDMD) cleavage and subsequent pyroptosis. Activated by cleavage by B.anthracis lethal toxin (LT) endopeptidase (PubMed:16429160, PubMed:24935976). Cleavage by LT 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 1b, C-terminus), which polymerizes and forms the Nlrp1b inflammasome (By similarity). Nlrp1b inflammasome is inhibited by DPP8 and DPP9, which sequester the C-terminal fragment of Nlrp1b (NACHT, LRR and PYD domains-containing protein 1b, C-terminus) in a ternary complex, thereby preventing Nlrp1b oligomerization and activation (By similarity). Nlrp1b inflammasome is activated by Val-boroPro (Talabostat, PT-100), an inhibitor of dipeptidyl peptidases DPP8 and DPP9 (PubMed:31383852). Val-boroPro relieves inhibition of DPP8 and/or DPP9 by promoting disruption of the ternary complex, releasing its C-terminal part from autoinhibition (By similarity). Activated by metabolic inhibitors, such as 2-deoxy-D-glucose and sodium azide (PubMed:24935976). Not activated by muramyl dipeptide, nor by full-length bacterial peptidoglycan (PubMed:24935976). Interacts with DPP9; leading to inhibit activation of the inflammasome (By similarity). DPP9 acts via formation of a ternary complex, composed of a DPP9 homodimer, one full-length Nlrp1b protein, and one cleaved C-terminus of Nlrp1b (NACHT, LRR and PYD domains-containing protein 1b, C-terminus) (By similarity). Interacts with DPP8; leading to inhibit activation of the inflammasome, probably via formation of a ternary complex with DPP8 (By similarity). Interacts (via LRR repeats) with BCL2 and BCL2L1 (via the loop between motifs BH4 and BH3). Interacts with NOD2; this interaction may increase IL1B release (By similarity). Interacts with EIF2AK2/PKR; this interaction requires EIF2AK2 activity, is accompanied by EIF2AK2 autophosphorylation and promotes inflammasome assembly in response to B.anthracis lethal toxin (By similarity). Interacts with MEFV; this interaction targets Nlrp1b to degradation by autophagy, hence preventing excessive IL1B- and IL18-mediated inflammation (By similarity). Interacts with the C-terminal part of Nlrp1b (NACHT, LRR and PYD domains-containing protein 1b, C-terminus) in absence of pathogens and other damage-associated signals. Interacts with the N-terminal part of Nlrp1b (NACHT, LRR and PYD domains-containing protein 1b, N-terminus) in absence of pathogens and other damage-associated signals (By similarity). Homomultimer; forms the Nlrp1b inflammasome polymeric complex, a filament composed of homopolymers of this form in response to pathogens and other damage-associated signals. The Nlrp1b inflammasome polymeric complex directly recruits pro-caspase-1 (proCASP1) independently of PYCARD/ASC. Interacts (via CARD domain) with CASP1 (via CARD domain); leading to CASP1 activation (By similarity). Expressed in macrophages. The CARD domain is involved in the interaction with CASP1 and CASP4/CASP11. 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. The FIIND (domain with function to find) region is involved in homomerization, but not in CASP1-binding. Autocatalytic cleavage in this region occurs constitutively, prior to activation signals, and is required for inflammasome activity (IL1B release), possibly by facilitating CASP1 binding. Both N- and C-terminal fragments remain associated. The C-terminal part of Nlrp1b oligomerizes to form the core of the Nlrp1b 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. The UPA region reduces the threshold needed for filament formation and signaling. Autocatalytically cleaved. Autocatalytic cleavage in FIIND region occurs constitutively, prior to activation signals, and is required for inflammasome activity (IL1B release), possibly by facilitating CASP1 binding. Both N- and C-terminal parts remain associated non-covalently. Ubiquitinated by the N-end rule pathway in response to pathogens and other damage-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 1b, C-terminus), which polymerizes and forms the Nlrp1b inflammasome. (Microbial infection) Cleavage by B.anthracis lethal toxin (LT) endopeptidase 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 1b, C-terminus), which polymerizes and forms the Nlrp1b inflammasome. Nlrp1b gene is extremely polymorphic. 5 alleles have been described in 18 inbred strains: 1 (AC Q2LKW6), 2 (AC A1Z198), 3 (AC Q2LKV5), 4 (AC Q2LKV2) and 5 (this entry). These alleles define susceptibility to B.anthracis lethal toxin (LT). Alleles 1 (carried by strains 129S1/SvImJ, BALB/cJ, C3H/HeJ, CBA/J, FVB/NJ, NON/ShiLtJ, NZO (NZO/HlLtJ) and SWR/J) and 5 (CAST/EiJ) confer macrophage susceptibility to LT. Strains with macrophages resistant to anthrax LT carry alleles 2 (A/J, C57BL/6J and I/LnJ), 3 (AKR/J, NOD/LtJ and SJL/J) or 4 (DBA/2J, P/J and SM/J). Sensitivity to LT leads to IL1B release, macrophage pyroptosis and neutrophil recruitment. This early inflammatory response confers increased resistance to infection by B. anthracis spores (PubMed:16429160). The sequence shown in this entry is that of allele 5 (PubMed:16429160). Three tandem Nrlp1 paralogs, Nrlp1a, Nrlp1b and Nrlp1c, have been identified. Nlrp1c is predicted to be a pseudogene. Neither Nlrp1a, nor Nrlp1c are expressed in anthrax lethal toxin susceptible strains, hence neither of them is thought to play an important role in this phenotype. 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.