AIF1 (allograft inflammatory factor 1) is a calcium-binding actin-bundling protein predominantly expressed in microglia and macrophages that plays crucial roles in immune cell function and inflammation. Mechanistically, AIF1 binds to and enhances the actin-bundling activity of L-fimbrin, facilitating actin reorganization in membrane ruffles and phagocytic cups 1. This interaction promotes cell migration and phagocytosis by microglia, while also enhancing RAC activation and lymphocyte migration. AIF1 expression marks activated microglial phenotypes associated with phagocytic activity in neurodegenerative settings 2. Clinically, AIF1 is implicated in multiple diseases including Alzheimer's disease, where altered microglial phenotypes express variable AIF1 levels depending on pathological context 3. Recent proteome-wide Mendelian randomization analysis identified AIF1 as a causal therapeutic target for ankylosing spondylitis, demonstrating shared genetic variation between elevated AIF1 plasma levels and disease risk 4. Additionally, AIF1-expressing dendritic cells play roles in tumor immunity, transporting T cell receptor clones during T cell differentiation in non-small cell lung cancer 5. AIF1's involvement in coordinating innate immune activation and phagocytosis positions it as a potential therapeutic target in inflammatory and neurodegenerative conditions, though pleiotropic effects require careful consideration.