FUNDC1 is an integral mitochondrial outer-membrane protein that coordinates multiple aspects of mitochondrial quality control and cellular homeostasis 1. Functionally, FUNDC1 mediates mitochondria-associated endoplasmic reticulum membrane (MAM) formation and regulates intracellular calcium signaling and VEGFR2 expression to influence angiogenesis 1. Its primary role involves hypoxia-induced mitophagy activation through direct interaction with LC3 protein family members, which it recruits to mitochondria 23. Mechanistically, FUNDC1 recruits DRP1 at ER-mitochondria contact sites to facilitate mitochondrial fission during hypoxia through promotion of DRP1 oligomerization and GTPase activity 4. In hepatic ferroptosis, FUNDC1 interacts with glutathione peroxidase-4 (GPx4) to facilitate its mitochondrial translocation via the TOM/TIM complex, where GPx4 undergoes mitophagy-mediated degradation 5. Disease relevance is substantial: FUNDC1 deficiency in endothelial cells drives pulmonary hypertension through impaired mitophagy and metabolic reprogramming toward aerobic glycolysis 6, while reduced FUNDC1 expression increases intestinal endothelial ferroptosis during ischemia-reperfusion injury 7. FUNDC1 dysregulation also contributes to sorafenib resistance in hepatocellular carcinoma 8. These findings establish FUNDC1 as a critical regulator of mitochondrial homeostasis with significant clinical implications for neurodegenerative, cardiovascular, and oncological diseases.