AIM2 (absent in melanoma 2) is a multifunctional DNA sensor protein that operates through both inflammasome-dependent and inflammasome-independent mechanisms. As a pattern recognition receptor, AIM2 detects cytosolic double-stranded DNA and mitochondrial DNA, initiating innate immune responses by assembling inflammasome complexes with ASC and caspase-1, leading to pyroptotic cell death and IL-1β/IL-18 secretion 123. Beyond inflammation, AIM2 functions as a tumor suppressor by restraining AKT-mTOR signaling through interaction with the RACK1-PP2A phosphatase complex, thereby suppressing cell proliferation 4. AIM2 plays a critical T cell-intrinsic role in regulatory T cell (Treg) stability by attenuating AKT phosphorylation and promoting lipid oxidation, thereby restraining autoimmunity 4. In psoriasis, AIM2 dysregulation—both inflammasome-dependent and inflammasome-independent pathways—contributes to excessive inflammation and altered immune cell function 5. AIM2 activation is tightly regulated by lipid metabolism; 25-hydroxycholesterol maintains mitochondrial integrity to prevent spurious inflammasome activation 6. These dual roles make AIM2 a potential therapeutic target for inflammatory diseases, autoimmunity, and cancer 17.