OPA1 is a mitochondrial inner membrane GTPase that regulates mitochondrial morphology and function through membrane fusion and cristae remodeling. Mechanistically, OPA1 embeds into cardiolipin-rich membranes via a lipid-binding paddle domain and forms helical oligomeric assemblies that drive inner mitochondrial membrane fusion and remodel cristae architecture 1. OPA1's GTPase activity is essential for its functions independent of structural fusion roles 2. Beyond fusion, OPA1 maintains mitochondrial homeostasis and oxidative phosphorylation capacity, supports anti-apoptotic signaling by preventing cytochrome c release, and regulates ferroptosis susceptibility through mitochondrial ROS generation and stress response suppression 23. OPA1 also coordinates with mitophagy machinery through interactions with FUNDC1 to balance mitochondrial dynamics and quality control 4. Clinically, OPA1 mutations cause dominant optic atrophy, the leading genetic cause of childhood blindness, plus neurodegenerative conditions including Behr syndrome and mitochondrial DNA depletion syndromes 5. OPA1 dysfunction impairs skeletal and cardiac muscle physiology and has been identified as therapeutically relevant in venetoclax-resistant acute myeloid leukemia and tumor angiogenesis, with small molecule OPA1 inhibitors showing potential for cancer treatment 67.