Simple SummaryAllograft inflammatory factor 1 (AIF1) is a calcium-binding protein that participates in intracellular processes such as phagocytosis, membrane ruffling and F-actin remodeling. Due to its multiple functions, AIF1 is linked with the activation of macrophages and several diseases such as kidney disease, rheumatoid arthritis, cancer, cardiovascular diseases, metabolic diseases, neurological disorders and transplants. In this review, we present a comprehensive review of the known structure, functions and role of AIF1 in inflammatory diseases.AbstractMacrophages are a type of immune cell distributed throughout all tissues of an organism. Allograft inflammatory factor 1 (AIF1) is a calcium-binding protein linked to the activation of macrophages. AIF1 is a key intracellular signaling molecule that participates in phagocytosis, membrane ruffling and F-actin polymerization. Moreover, it has several cell type-specific functions. AIF1 plays important roles in the development of several diseases: kidney disease, rheumatoid arthritis, cancer, cardiovascular diseases, metabolic diseases and neurological disorders, and in transplants. In this review, we present a comprehensive review of the known structure, functions and role of AIF1 in inflammatory diseases.