Aim2, also known as Absent in melanoma 2, is a cytoplasmic sensor that recognizes double-strand DNA. It is a key component of the inflammasome, a protein platform initiating innate immune responses. By cleaving pro-caspase-1, Aim2 converts IL-1β and IL-18 to their mature forms, and promotes pyroptosis by converting Gasdermin-D to GSDMD-N fragments. Aim2 is involved in multiple biological processes related to innate immunity and inflammatory cell death [1,2].

In lupus, AIM2 deficiency in B cells reduces the frequency of CD19+ B-cells, dampens antibody production, and attenuates lupus symptoms. It is found to be an upstream regulator of Blimp-1 and Bcl-6, which are important in B-cell differentiation [3].

In rhabdomyolysis-induced acute kidney injury, Aim2-deficiency leads to macrophage accumulation, delayed kidney functional recovery, and aggravated inflammation. Macrophages with intact Aim2 undergo pyroptosis in response to dsDNA, which potentially serves as an anti-inflammatory program [5].

In renal cell carcinoma, AIM2 promotes cancer progression and sunitinib resistance through inhibiting ferroptosis by regulating the FOXO3a-ACSL4 axis [4].

In conclusion, Aim2 plays crucial roles in innate immunity, inflammation, and disease development. Gene knockout models, especially in B cells and macrophages, have revealed its functions in autoimmune diseases like lupus, kidney injury, and cancer. Understanding Aim2 provides insights into disease mechanisms and potential therapeutic targets for related conditions.