IFI44L (interferon induced protein 44 like) is a type I interferon-stimulated gene (ISG) that functions as a critical antiviral and antibacterial effector protein 1. As an ISG, IFI44L exhibits antiviral activity against multiple viruses including hepatitis C virus, though with relatively low potency compared to other ISGs 1. During bacterial infections, IFI44L promotes macrophage differentiation and facilitates inflammatory cytokine secretion 2. The protein is highly expressed in autoimmune diseases, particularly systemic lupus erythematosus (SLE) and rheumatoid arthritis, where it serves as a shared molecular marker 34. Epigenetic regulation plays a key role in IFI44L function, with promoter hypomethylation associated with increased expression in SLE and RA patients 5. Genetic variants in IFI44L are associated with variable susceptibility to respiratory tract infections in children, with certain variants providing protective effects against acute otitis media and reducing antibiotic usage 6. In cancer contexts, IFI44L expression is upregulated by ACSL4 through interferon signaling pathways involving JAK1, TYK2, STAT1, and IRF1, promoting cell proliferation and invasiveness in head and neck squamous cell carcinoma 7. The protein localizes to the cytosol and participates in immune response regulation.