IFNA21 is a type I interferon produced by macrophages with pleiotropic immune and antiviral functions 1. As a member of the interferon alpha gene cluster on chromosome 9, IFNA21 exerts cytokine activity through type I interferon receptor binding and stimulates production of antiviral enzymes including protein kinase and oligoadenylate synthetase 2. IFNA21 modulates adaptive immunity by activating B cells, T cells, and natural killer cells, and participates in type I interferon-mediated signaling pathways 3. In cancer biology, IFNA21 expression patterns have significant prognostic implications. In glioma, reduced IFNA21 expression correlates with worse overall survival, higher tumor grades, and immune dysregulation within the tumor microenvironment 1. In cholangiocarcinoma, IFNA21 acts as a pro-tumoral inflammatory marker whose downregulation enhances anti-folate receptor alpha CAR-T cell therapy efficacy 4. IFNA21 also contributes to inflammatory disease pathogenesis. Elevated serum IFNA21 levels associate with coronary artery disease risk, particularly in females, with certain 9p21 SNPs modulating IFNA21-mediated inflammatory processes 2. Genome-wide association studies identified IFNA21 as a melanoma susceptibility gene within immune cytokine signaling pathways 3. Additionally, rare IFNA21 variants are associated with multisystem inflammatory syndrome in children, suggesting involvement in innate immune errors 5.