FUNDC2 is a mitochondrial outer membrane protein that functions as a PIP3-binding protein and regulator of mitochondrial dynamics with broad implications in cancer and cell survival. Mechanistically, FUNDC2 binds phosphatidylinositol-3,4,5-trisphosphate (PIP3) via its N-terminal motif, enabling PIP3 recruitment to mitochondria and activation of downstream AKT signaling 1. FUNDC2 also directly interacts with mitofusin 1 (MFN1), inhibiting its GTPase activity to suppress mitochondrial fusion, thereby promoting mitochondrial fragmentation 2. Clinically, FUNDC2 is upregulated in approximately 40% of hepatocellular carcinomas and multiple other cancer types, with elevated expression inversely correlating with patient survival 23. In triple-negative breast cancer, FUNDC2 overexpression promotes cell proliferation, migration, and invasion through AKT/GSK3β/GLI1 pathway activation 4. Beyond cancer, FUNDC2 is essential for platelet survival under stress conditions via the PIP3/AKT/BCL-xL axis 1, and platelet mitochondria expressing FUNDC2 can be therapeutically transplanted to rescue ischemia/reperfusion injury through FUNDC2/PIP3/AKT/FOXO3a signaling 5. These findings position FUNDC2 as a potential therapeutic target in cancer and ischemic injury.