OAS3 (2'-5'-oligoadenylate synthetase 3) is an interferon-induced, dsRNA-activated antiviral enzyme that synthesizes 2'-5'-oligoadenylates (2-5A) from ATP, which activate ribonuclease L (RNase L) to degrade viral and cellular RNA and inhibit protein synthesis 1. OAS3 functions through both classical RNase L-dependent and alternative antiviral pathways, displaying activity against multiple viruses including Dengue and Chikungunya [UniProt summary]. Beyond antiviral defense, OAS3 participates in immune regulation and disease pathology. In pancreatic cancer, lactate-induced OAS3 upregulation promotes M2d macrophage polarization, suppressing anti-tumor immunity; OAS3 targeting restores CD8+ T-cell cytotoxicity 1. In sepsis-induced acute lung injury, TRIM21 downregulation increases OAS3 protein levels, promoting epithelial cell apoptosis via RNase L activation 2. OAS3 dysregulation appears relevant across multiple diseases: genetic variants associate with critical COVID-19 illness 3, elevated levels serve as biomarkers for systemic lupus erythematosus diagnosis and activity 4, and IRF2-driven upregulation promotes acute myeloid leukemia progression through JAK-STAT pathway modulation 5. In type 1 diabetes, m6A-mediated OAS3 regulation controls innate immune response amplitude 6. These findings establish OAS3 as a critical hub regulating antiviral and inflammatory responses with therapeutic implications across infectious, autoimmune, and malignant diseases.