NAIF1 (Nuclear Apoptosis Inducing Factor 1) is a nuclear protein that functions as a tumor suppressor by inducing apoptosis and inhibiting cancer cell proliferation, migration, and invasion 1. The protein contains a homeodomain-like region and nuclear localization signals, and is conserved across multiple species 1. NAIF1 induces apoptosis primarily through the intrinsic mitochondrial pathway, activating procaspase-9 followed by caspase-3, while decreasing mitochondrial membrane potential 21. The N-terminal 1-90 amino acid domain containing a helix-turn-helix motif is sufficient for apoptotic induction 2. NAIF1 expression is significantly downregulated in multiple cancer types including gastric cancer, osteosarcoma, and prostate cancer, where reduced expression correlates with poor differentiation and advanced tumor stages 23. The protein inhibits cancer cell migration and invasion through MAPK pathway modulation, reducing MMP2/MMP9 expression and inhibiting FAK activation 4. NAIF1 is regulated by several microRNAs including miR-128, miR-125a-5p, and miR-29b, which target its 3'-UTR and suppress its tumor suppressor functions 356. These findings suggest NAIF1 may serve as a potential therapeutic target for cancer treatment.