COX7A1 is a nuclear-encoded subunit of mitochondrial cytochrome c oxidase (Complex IV), the terminal enzyme of the electron transport chain that catalyzes oxygen reduction to water 1. As a component of respiratory Complex IV, COX7A1 drives oxidative phosphorylation and participates in mitochondrial energy generation 2. Functionally, COX7A1 acts as an assembly factor promoting homodimerization of Complex IV and formation of mitochondrial respirasomes (supercomplexes containing two COX units), which enhance respiratory chain efficiency 2. COX7A1 expression is reversibly regulated by metabolic state: it preferentially supports oxidative phosphorylation under glycolytic conditions through distinct mitochondrial respiratory chain organization 2. In skeletal muscle, COX7A1 expression associates with glucose uptake and aerobic capacity (VO2max), though age-related epigenetic changes via promoter DNA methylation reduce expression in elderly individuals 3. COX7A1 exists as a muscle-specific isoform (VIIa-M) regulated by tissue-specific transcription factors 1. Beyond normal metabolism, COX7A1 overexpression enhances ferroptosis sensitivity in lung cancer cells through increased mitochondrial TCA cycle activity and Complex IV function, while suppressing autophagy 4, 5. These findings suggest COX7A1's potential as a therapeutic target in cancer metabolic pathways.