AIM2

AIM2, Absent in Melanoma 2, is a human cytosolic sensor of double-stranded DNA and a member of the AIM2-like receptor (ALR) family. It functions as a key component of the inflammasome, forming with the adaptor protein ASC and caspase-1 to trigger inflammatory responses. Upon detection of dsDNA in the cytosol, AIM2 binds DNA via its C-terminal HIN-200 domain and recruits ASC through its N-terminal pyrin domain, assembling an inflammasome complex.

AIM2 contains a C-terminal HIN-200 domain for DNA binding and an N-terminal pyrin domain that mediates interaction with ASC. This domain organization enables rapid assembly of the AIM2 inflammasome when cytosolic DNA is present.

Once formed, the inflammasome activates caspase-1, which cleaves pro-IL-1β and pro-IL-18, promoting their secretion; caspase-1 also cleaves gasdermin D to form membrane pores and induce pyroptosis.

AIM2 contributes to defense against intracellular bacteria and DNA viruses; it also detects damaged self-DNA, contributing to sterile inflammation in tissues such as skin and gut.

In humans, AIM2 signaling is linked to autoinflammatory diseases and cancer biology; context-dependent roles include tumor-suppressive effects in colorectal cancer; researchers are exploring AIM2 as a target to modulate inflammasome-driven diseases.