COA3 is a core component of the MITRAC complex that regulates cytochrome c oxidase (COX/Complex IV) assembly in mitochondria. It functions as a mitochondrial inner membrane assembly factor essential for efficient translation of the mitochondrial-encoded COX1 subunit and subsequent assembly of the respiratory chain Complex IV 1. COA3 exists in an early COX assembly intermediate with COX1 and other assembly factors including COX14, forming a complex that stabilizes newly synthesized COX1 before incorporation of nuclear-encoded subunits 2. The protein exhibits oligomeric behavior with high conformational flexibility, a structural feature crucial for protein-protein interactions and mitochondrial protein assembly 3. Mutations in COA3 cause isolated Complex IV deficiency associated with neuropathy, exercise intolerance, obesity, and short stature 1. Defective COX1 translation due to COA3 loss triggers reactive oxygen species-induced inflammation, particularly in liver tissue 4. Clinically, COA3 overexpression in non-small cell lung cancer promotes metastasis through glucose metabolism reprogramming and mitochondrial fragmentation, making it a potential prognostic marker 5. Genetic studies suggest COA3 acts as a protective factor against osteoarthritis development 6.