MESEYREMLLLTGLDHITEEELKRFKYFALTEFQIARSTLDVADRTELADHLIQSAGAASAVTKAINIFQKLNYMHIANALEEKKKEAERKLMTNTKKRGTQKVENRSQAENCSAASATRSDNDFKEQAATEVCPQAKPQKKQMVAEQEAIREDLQKDPLVVTVLKAINPFECETQEGRQEIFHATVATETDFFFVKVLNAQFKDKFIPKRTIKISNYLWHSNFMEVTSSSVVVDVESNHEVPNNVVKRARETPRISKLKIQPCGTIVNGLFKVQKITEEKDRVLYGIHDKTGTMEVLVLGNPSKTKCEEGDKIRLTFFEVSKNGVKIQLKSGPCSFFKVIKAAKPKTDMKSVE

Sensor component of the AIM2 inflammasome, which mediates inflammasome activation in response to the presence of double-stranded DNA (dsDNA) in the cytosol, leading to subsequent pyroptosis (PubMed:19158679, PubMed:19131592, PubMed:20351692, PubMed:19158675, PubMed:19158676, PubMed:20351693, PubMed:20417169, PubMed:20457908, PubMed:21902795, PubMed:32350463, PubMed:34006824, PubMed:23567559). 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:19131592, PubMed:20351692, PubMed:19158675, PubMed:19158676, PubMed:20351693, PubMed:20417169, PubMed:20457908, PubMed:21902795, PubMed:23567559, PubMed:32350463). Acts as a recognition receptor (PRR): specifically recognizes and binds dsDNA in the cytosol, and mediates the formation of the inflammasome polymeric complex composed of AIM2, CASP1 and PYCARD/ASC (PubMed:19131592, PubMed:20351692, PubMed:19158675, PubMed:19158676, PubMed:20351693, PubMed:20417169, PubMed:20457908, PubMed:21902795, PubMed:23567559). Recruitment of pro-caspase-1 (proCASP1) to the AIM2 inflammasome promotes caspase-1 (CASP1) activation, which subsequently cleaves and activates inflammatory cytokines IL1B and IL18 and gasdermin-D (GSDMD), promoting cytokine secretion (PubMed:19158676). In some cells, CASP1 activation mediates cleavage and activation of GSDMD, triggering pyroptosis without promoting cytokine secretion (PubMed:27846608, PubMed:32350463). Detects cytosolic dsDNA of viral and bacterial origin in a non-sequence-specific manner (PubMed:19131592, PubMed:19158675, PubMed:20351692, PubMed:23567559). Involved in the DNA damage response caused by acute ionizing radiation by mediating pyroptosis of intestinal epithelial cells and bone marrow cells in response to double-strand DNA breaks (PubMed:27846608). Mechanistically, AIM2 senses DNA damage in the nucleus to mediate inflammasome assembly and inflammatory cell death (PubMed:27846608). Also acts as a regulator of neurodevelopment via its role in the DNA damage response: acts by promoting neural cell death in response to DNA damage in the developing brain, thereby purging genetically compromised cells of the central nervous system (PubMed:32350463). Pyroptosis mediated by the AIM2 inflammasome in response to DNA damage is dependent on GSDMD without involving IL1B and IL18 cytokine secretion (PubMed:27846608, PubMed:32350463). Also acts as a mediator of pyroptosis, necroptosis and apoptosis (PANoptosis), an integral part of host defense against pathogens, in response to bacterial infection (PubMed:34471287). Can also trigger PYCARD/ASC-dependent, caspase-1-independent cell death that involves caspase-8 (CASP8) (PubMed:22555457).