COA8 (cytochrome c oxidase assembly factor 8) is a mitochondrial protein essential for the assembly and function of cytochrome c oxidase (complex IV), the terminal component of the electron transport chain 1. The protein localizes to the matrix side of the mitochondrial inner membrane and protects COX from oxidative damage by stabilizing the complex during assembly 1. COA8 exhibits unique redox-sensitive regulation: under normal conditions, it is rapidly degraded by the ubiquitin-proteasome system, but oxidative stress stabilizes the protein, increasing its mature intramitochondrial form and enhancing COX protection 12. Loss-of-function mutations in COA8 cause mitochondrial complex IV deficiency, nuclear type 17, characterized by cavitating leukoencephalopathy with distinctive neuroimaging features and neurological deterioration 34. Animal models demonstrate that COA8 deficiency leads to impaired motor coordination, reduced COX activity across multiple tissues, and shortened lifespan under oxidative stress conditions 14. Recent studies have also implicated COA8 variants in cognitive performance and age-related hearing loss, suggesting broader roles in neurological function 56. The protein represents a critical link between cellular redox homeostasis and mitochondrial respiratory function.