COX6A2 is a structural subunit of cytochrome c oxidase (Complex IV), the terminal enzyme of the mitochondrial electron transport chain that catalyzes oxygen reduction to water and drives oxidative phosphorylation 1. Located on chromosome 16, COX6A2 plays critical roles in Complex IV assembly and stabilization while maintaining energy homeostasis in tissues with high metabolic demands, particularly heart, skeletal muscle, and parvalbumin-positive fast-spiking interneurons 2. In parvalbumin interneurons, COX6A2 protects against oxidative stress and supports ATP generation necessary for high-frequency firing activity 2. COX6A2 deficiency impairs interneuron maturation, disrupts perineuronal nets, and associates with neurological abnormalities 2. In cardiomyocytes, COX6A2 knockout causes abnormal energy metabolism, elevated oxidative stress, calcium transport dysfunction, and reduced contractility 3. COX6A2 mutations cause mitochondrial complex IV deficiency with myopathic and potential neurological manifestations 4. Dysregulation also occurs in type 2 diabetes, where reduced FXR expression increases COX6A2 levels, promoting pancreatic β-cell apoptosis through VDAC1-mediated mitochondrial Bax translocation 5. In schizophrenia, oxidative stress-induced miR-137 upregulation decreases COX6A2 expression and impairs mitophagy, correlating with parvalbumin interneuron dysfunction 6. These findings establish COX6A2 as a metabolic regulator with disease relevance spanning mitochondrial myopathies, neuropsychiatric disorders, and metabolic disease.