COX17 is a mitochondrial copper metallochaperone essential for cytochrome c oxidase (Complex IV) assembly in the respiratory chain 1. COX17 binds two copper ions and delivers them to downstream chaperones: SCO1 and SCO2, which direct copper to the Cu(A) site on COX2, and COX11, which relays copper to the Cu(B) site on COX1 2. Mechanistically, COX17 acetylation by the MOF-KANSL complex promotes its copper delivery function and maintains Complex IV integrity and mitochondrial electron transport chain activity 3. In peripheral tissues, COX17 functions as a central copper chaperone targeting cuprous ions to oxidative phosphorylation pathways 4. Clinically, COX17 dysfunction is relevant to metabolic disorders and cancer progression. COX17 knockdown disrupts cytochrome c oxidase assembly and supercomplex organization, preventing normal respiratory complex biogenesis 2. In triple-negative breast cancer, COX17 depletion phenocopies copper chelation therapy effects, impairing Complex IV activity and metastatic capacity through AMPK/mTORC1 pathway modulation 5. While COX17 mutations are rare in COX deficiency patients 6, dysregulation of COX17 expression contributes to cancer progression and represents a potential therapeutic target 7.