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:27281216). 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:27281216). Promotes pyroptosis in response to microbial infection and danger signals (PubMed:26375003, PubMed:26375259, PubMed:27418190, PubMed:28392147, PubMed:32820063). Produced by the cleavage of gasdermin-D by inflammatory caspases CASP1, CASP4 or CASP5 in response to canonical, as well as non-canonical (such as cytosolic LPS) inflammasome activators (PubMed:26375003, PubMed:26375259, 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:27281216, PubMed:29898893). 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:27418190, PubMed:27281216, PubMed:29898893, PubMed:33883744). Exhibits bactericidal activity (PubMed:27281216). 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:27281216). Under cell culture conditions, also active against intracellular bacteria, such as Listeria monocytogenes (By similarity). Also active in response to MAP3K7/TAK1 inactivation by Yersinia toxin YopJ, which triggers cleavage by CASP8 and subsequent activation (By similarity). Strongly binds to bacterial and mitochondrial lipids, including cardiolipin (PubMed:27281216). Does not bind to unphosphorylated phosphatidylinositol, phosphatidylethanolamine nor phosphatidylcholine (PubMed:27281216). 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:28928145, PubMed:29576317, PubMed:32109412). The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-D, N-terminal) following cleavage by caspases CASP1, CASP4, CASP5 or CASP8 (PubMed:26375003, PubMed:26375259, PubMed:27418190, PubMed:29898893, PubMed:32109412). Cleavage at Asp-87 by CASP3 or CAPS7 inactivates the ability to mediate pyroptosis (PubMed:28392147). Homooligomer; homooligomeric ring-shaped pore complex containing 27-28 subunits when inserted in the membrane (PubMed:33883744). In response to a canonical inflammasome stimulus, such as nigericin, recruited to NLRP3 inflammasone with similar kinetics to that of uncleaved CASP1 precursor (By similarity). Although this recruitment is also observed in the absence of PYCARD, it is more efficient in its presence (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. Released in the extracellular milieu following pyroptosis. Expressed in the suprabasal cells of esophagus, as well as in the isthmus/neck, pit, and gland of the stomach, suggesting preferential expression in differentiating cells. Intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of cleavage by inflammatory caspases CASP1, CASP4 or CASP5 (PubMed:26375003, PubMed:29898893, PubMed:28928145, PubMed:29576317). The linker helix loop inserts into the N-terminal domain (PubMed:28928145). The intrinsic pyroptosis-inducing activity is carried by Gasdermin-D, N-terminal, that is released upon cleavage by inflammatory caspases (PubMed:26375003). Forms a ring-shaped pore complex containing 27-28 subunits that inserts into the membrane (PubMed:33883744). The pore conduit is predominantly negatively charged, facilitating the release of mature interleukin-1 (IL1B and IL18) (PubMed:33883744). In contrast interleukin-1 precursors are not released, due to the presence of an acidic region that is proteolytically removed by CASP1 during maturation (PubMed:33883744). Cleavage at Asp-275 by CASP1 (mature and uncleaved precursor forms), CASP4, CASP5 or CASP8 relieves autoinhibition and is sufficient to initiate pyroptosis (PubMed:26375003, PubMed:29898893, PubMed:32109412). Cleavage by CASP1 and CASP4 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:32109412). Cleavage by CASP8 takes place following inactivation of MAP3K7/TAK1 by Yersinia toxin YopJ (By similarity). Cleavage at Asp-87 by CASP3 or CAPS7 inactivates the ability to mediate pyroptosis (PubMed:28392147, PubMed:28045099). Succination of Cys-191 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). Belongs to the gasdermin family.