FUNCTION Precursor of a pore-forming protein that converts non-inflammatory apoptosis to pyroptosis (PubMed:27281216, PubMed:28459430, PubMed:33852854, PubMed:35594856, PubMed:36607699). This form constitutes the precursor of the pore-forming protein: upon cleavage, the released N-terminal moiety (Gasdermin-E, N-terminal) binds to membranes and forms pores, triggering pyroptosis (PubMed:28459430).FUNCTION Pore-forming protein produced by cleavage by CASP3 or granzyme B (GZMB), which converts non-inflammatory apoptosis to pyroptosis or promotes granzyme-mediated pyroptosis, respectively (PubMed:27281216, PubMed:28459430, PubMed:32188940, PubMed:33852854, PubMed:35594856). After cleavage, moves to the plasma membrane, homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, allowing the release of mature interleukins (IL1B and IL16) and triggering pyroptosis (PubMed:28459430, PubMed:32188940, PubMed:33852854, PubMed:35594856). Binds to inner leaflet lipids, bisphosphorylated phosphatidylinositols, such as phosphatidylinositol (4,5)-bisphosphate (PubMed:28459430). Cleavage by CASP3 switches CASP3-mediated apoptosis induced by TNF or danger signals, such as chemotherapy drugs, to pyroptosis (PubMed:27281216, PubMed:28459430, PubMed:32188940). Mediates secondary necrosis downstream of the mitochondrial apoptotic pathway and CASP3 activation as well as in response to viral agents (PubMed:28045099). Exhibits bactericidal activity (PubMed:27281216). Cleavage by GZMB promotes tumor suppressor activity by triggering robust anti-tumor immunity (PubMed:21522185, PubMed:32188940). Suppresses tumors by mediating granzyme-mediated pyroptosis in target cells of natural killer (NK) cells: cleavage by granzyme B (GZMB), delivered to target cells from NK-cells, triggers pyroptosis of tumor cells and tumor suppression (PubMed:31953257, PubMed:32188940). May play a role in the p53/TP53-regulated cellular response to DNA damage (PubMed:16897187).FUNCTION (Microbial infection) Pore-forming protein, which promotes maternal placental pyroptosis in response to Zika virus infection, contributing to adverse fetal outcomes.ACTIVITY REGULATION 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:28045099, PubMed:28459430). The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-E, N-terminal) following cleavage by CASP3 or granzyme B (GZMB) (PubMed:28459430, PubMed:31953257, PubMed:32188940, PubMed:35594856). Activated by NLRP1 in the absence of GSDMD expression: NLRP1 cleaves and activates CASP8, promoting downstream activation of CASP3 and subsequent activation of GSDME (PubMed:33852854, PubMed:35594856).ACTIVITY REGULATION (Microbial infection) Activated upon human coronavirus SARS-CoV-2 infection, leading to lung epithelial cell death (PubMed:35594856). Activation takes place in response to (1) activation of NLRP1 and (2) inactivation of GSDMD following NLRP1 and GSDMD cleavage by the SARS-CoV-2 3C-like proteinase nsp5 (PubMed:35594856).SUBUNIT Homooligomer; homooligomeric ring-shaped pore complex containing 27-28 subunits when inserted in the membrane.INTERACTION Expressed in cochlea (PubMed:9771715). Low level of expression in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas, with highest expression in placenta (PubMed:9771715).DOMAIN Intramolecular interactions between N- and C-terminal domains may be important for autoinhibition in the absence of activation signal. The intrinsic pyroptosis-inducing activity is carried by the N-terminal domain, that is released upon cleavage by CASP3 or granzyme B (GZMB).PTM Cleavage at Asp-270 by CASP3 (mature and uncleaved precursor forms) or granzyme B (GZMB) relieves autoinhibition and is sufficient to initiate pyroptosis.PTM Succination 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).PTM Ubiquitinated at Lys-120 and Lys-189 via 'Lys-48'-linked polyubiquitin chains, leading to proteasomal degradation. Deubiquitinated by USP48, leading to increased stability.PTM Palmitoylated.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE Is a tumor suppressor gene with an important role in colorectal cancer (CRC).SIMILARITY Belongs to the gasdermin family.SEQUENCE CAUTION Truncated N-terminus.