XAF1 (XIAP-associated factor 1) is a zinc-rich interferon-induced protein that functions as a negative regulator of anti-apoptotic proteins, particularly XIAP/BIRC4. XAF1 promotes apoptosis through multiple mechanisms: it induces caspase-independent cleavage and inactivation of BIRC4, facilitates mitochondrial translocation of BAX, and mediates cytochrome c release 1. XAF1 expression is regulated circadianly by microRNA-21, with elevated XAF1 levels promoting TNF-, FAS-, and perforin/granzyme-induced apoptosis in immune cells 123. In infectious disease contexts, XAF1 is upregulated during COVID-19 and tuberculosis infections, contributing to T cell apoptosis and immune dysregulation 324. Paradoxically, XAF1 exhibits context-dependent oncogenic functions: in colorectal cancer, XAF1 acts as a VCP adaptor promoting metastasis via the VCP-RNF114-JUP signaling axis 5. Additionally, XAF1 repression by LRP1-mediated signaling suppresses breast cancer metastasis, suggesting XAF1 as a metastasis-promoting factor in this context 6. These findings indicate XAF1 serves dual roles: promoting protective apoptosis in normal and infected cells while facilitating cancer cell metastasis through distinct molecular mechanisms.