IFI6 (interferon alpha inducible protein 6) is an interferon-stimulated gene that functions as a multifaceted regulator of antiviral immunity and cell survival. As a primary antiviral effector, IFI6 demonstrates broad-spectrum activity against multiple viruses through distinct mechanisms: it inhibits flavivirus replication by preventing endoplasmic reticulum membrane invaginations required for viral replication 1, reduces hepatitis C virus entry by suppressing EGFR signaling 1, and restricts hepatitis B virus replication through nuclear inhibition of viral promoter activity 2. IFI6 modulates innate immune responses by preventing RIG-I activation, thereby fine-tuning interferon signaling 3. Regarding apoptosis, IFI6 exhibits context-dependent roles: it negatively regulates intrinsic apoptotic pathways and mitochondrial depolarization, yet can also promote pro-apoptotic responses depending on cellular context. Clinically, IFI6 is elevated in systemic lupus erythematosus, suggesting a role in autoimmune pathogenesis 4. In cancer biology, IFI6 overexpression—stabilized by the AHSA1-HSP90AA1 complex—enhances Osimertinib resistance in EGFR-mutated lung adenocarcinoma by promoting mitochondrial stability and epithelial-mesenchymal transition 5. These findings position IFI6 as both a protective innate immune factor and a potential oncogenic contributor warranting further investigation as a therapeutic target.