Precursor of a pore-forming protein that plays a key role in host defense against pathogen infection and danger signals (PubMed:26375003, PubMed:26375259, PubMed:26611636, PubMed:27383986, PubMed:27385778, PubMed:27418190). This form constitutes the precursor of the pore-forming protein: upon cleavage, the released N-terminal moiety (Gasdermin-D, N-terminal) binds to membranes and forms pores, triggering pyroptosis (PubMed:26375003, PubMed:26375259, PubMed:26611636, PubMed:27383986, PubMed:27385778, PubMed:27418190). Promotes pyroptosis in response to microbial infection and danger signals (PubMed:26375003, PubMed:26375259, PubMed:26611636, PubMed:27383986, PubMed:27385778, PubMed:27418190, PubMed:32820063). Produced by the cleavage of gasdermin-D by inflammatory caspases CASP1 or CASP4/CASP11 in response to canonical, as well as non-canonical (such as cytosolic LPS) inflammasome activators (PubMed:26375003, PubMed:26375259, PubMed:26611636, PubMed:27383986, PubMed:27385778, PubMed:27418190). After cleavage, moves to the plasma membrane where it strongly binds to inner leaflet lipids, including monophosphorylated phosphatidylinositols, such as phosphatidylinositol 4-phosphate, bisphosphorylated phosphatidylinositols, such as phosphatidylinositol (4,5)-bisphosphate, as well as phosphatidylinositol (3,4,5)-bisphosphate, and more weakly to phosphatidic acid and phosphatidylserine (PubMed:27383986, PubMed:27339137). Homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, allowing the release of mature interleukin-1 (IL1B and IL18) and triggering pyroptosis (PubMed:27383986, PubMed:29274245, PubMed:29195811, PubMed:33883744). Exhibits bactericidal activity (PubMed:27383986). Gasdermin-D, N-terminal released from pyroptotic cells into the extracellular milieu rapidly binds to and kills both Gram-negative and Gram-positive bacteria, without harming neighboring mammalian cells, as it does not disrupt the plasma membrane from the outside due to lipid-binding specificity (PubMed:27383986). Under cell culture conditions, also active against intracellular bacteria, such as Listeria monocytogenes (PubMed:27383986). Also active in response to MAP3K7/TAK1 inactivation by Yersinia toxin YopJ, which triggers cleavage by CASP8 and subsequent activation (PubMed:30361383, PubMed:30381458). Strongly binds to bacterial and mitochondrial lipids, including cardiolipin. Does not bind to unphosphorylated phosphatidylinositol, phosphatidylethanolamine nor phosphatidylcholine (PubMed:27383986). The full-length protein before cleavage is inactive: intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of activation signal (PubMed:26375003, PubMed:26375259, PubMed:26611636, PubMed:29576317, PubMed:31097341). The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-D, N-terminal) following cleavage by inflammatory caspases CASP1, CASP4/CASP11 or CASP8 (PubMed:26375003, PubMed:26375259, PubMed:26611636, PubMed:30361383, PubMed:30381458, PubMed:32554464, PubMed:32553275). Cleavage at Asp-88 by CASP3 or CAPS7 inactivates the ability to mediate pyroptosis (By similarity). Homooligomer; homooligomeric ring-shaped pore complex containing 27-28 subunits when inserted in the membrane (By similarity). In response to a canonical inflammasome stimulus, such as nigericin, recruited to NLRP3 inflammasone with similar kinetics to that of uncleaved CASP1 precursor (PubMed:26611636). Although this recruitment is also observed in the absence of PYCARD, it is more efficient in its presence (PubMed:26611636). In response to a canonical inflammasome stimulus, such as nigericin, recruited to NLRP3 inflammasone with similar kinetics to that of uncleaved CASP1 precursor. Released in the extracellular milieu following pyroptosis. Expression starts at 8.5 dpc and increases from 13.5 dpc on. Still detected after birth. Intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of cleavage by inflammatory caspases CASP1 or CASP4/CASP11 (PubMed:26375003, PubMed:26375259, PubMed:26611636, PubMed:29576317, PubMed:31097341). The linker helix loop inserts into the N-terminal domain (By similarity). The intrinsic pyroptosis-inducing activity is carried by Gasdermin-D, N-terminal, that is released upon cleavage by inflammatory caspases (PubMed:26375003, PubMed:26375259, PubMed:26611636). Forms a ring-shaped pore complex containing 27-28 subunits that inserts into the membrane. The pore conduit is predominantly negatively charged, facilitating the release of mature interleukin-1 (IL1B and IL18). In contrast interleukin-1 precursors are not released, due to the presence of an acidic region that is proteolytically removed by CASP1 during maturation. Cleavage at Asp-276 by CASP1 (mature and uncleaved precursor forms), CASP4/CASP11 or CASP8 relieves autoinhibition and is sufficient to initiate pyroptosis (PubMed:26375259, PubMed:26611636, PubMed:32554464, PubMed:32553275). Cleavage by CASP1 and CASP4/CASP11 is not strictly dependent on the consensus cleavage site on GSDMD but depends on an exosite interface on CASP1 that recognizes and binds the Gasdermin-D, C-terminal (GSDMD-CT) part (PubMed:32554464, PubMed:32553275). Cleavage by CASP8 takes place following inactivation of MAP3K7/TAK1 by Yersinia toxin YopJ (PubMed:30361383, PubMed:30381458). Cleavage at Asp-88 by CASP3 or CAPS7 inactivates the ability to mediate pyroptosis (By similarity). Succination of Cys-192 by the Krebs cycle intermediate fumarate, which leads to S-(2-succinyl)cysteine residues, inhibits processing by caspases, and ability to initiate pyroptosis (PubMed:32820063). Succination modification is catalyzed by a non-enzymatic reaction caused by an accumulation of fumarate (PubMed:32820063). Knockout mice are born at the expected Mendelian rate and do not exhibit any overt phenotype in normal housing conditions. The gastrointestinal tract develops normally. They are however resistant to LPS-induced lethal septic shock. Primary bone marrow-derived macrophages fail to undergo pyroptosis in response to canonical (acting via CASP1), as well as to non-canonical (acting via CASP4) inflammasome activators. CASP1-mediated IL1B release is also impaired, but not CASP1 autoprocessing, nor IL1B maturation. Belongs to the gasdermin family.