COA6 (cytochrome c oxidase assembly factor 6) is a mitochondrial intermembrane space protein essential for the biogenesis of cytochrome c oxidase (complex IV) of the respiratory chain 1. COA6 specifically participates in copper delivery to the CuA site of the COX2 subunit, functioning as a disulfide reductase that reduces SCO and COX2 proteins during CuA site assembly 1. The protein contains a twin CX9C motif that enables copper binding properties crucial for complex IV biogenesis 2. Pathogenic mutations in COA6 cause fatal infantile mitochondrial complex IV deficiency disorders, highlighting its biomedical significance 1. Beyond its assembly function, COA6 has emerged as a cancer biomarker with prognostic value across multiple cancer types. In lung adenocarcinoma, elevated COA6 expression correlates with poor overall survival, advanced tumor stage, and reduced immune cell infiltration 3. Similarly, in pancreatic ductal adenocarcinoma, COA6 overexpression enhances cell proliferation, migration, and chemoresistance while modulating the immunosuppressive tumor microenvironment 4. COA6 appears to facilitate metabolic reprogramming between glycolysis and oxidative phosphorylation in cancer cells, supporting tumor progression and therapeutic resistance 4. These findings suggest COA6 represents a promising therapeutic target for cancer treatment.