Herein, we provide an overview of the emerging research progress on the function and regulatory pathway of absent in melanoma 2 (AIM2) in innate and adaptive immune cells, as well as tumor cells, and discuss its pathogenic role in autoimmune diseases, such as systemic lupus erythematosus, psoriasis, primary Sjogren's syndrome, and cancers, such as melanomas, non‐small‐cell lung cancer, colon cancer, hepatocellular carcinoma, renal carcinoma, and so on, hopefully providing potential therapeutic and diagnostic strategies for clinical use. This evidence concerns the gene AIM2 and systemic lupus erythematosus.