The cytochrome c oxidase (COX) family of proteins function as the final electron donor in the respiratory chain to drive a proton gradient across the inner mitochondrial membrane, ultimately resulting in the production of water. The mammalian COX apoenzyme is a dimer, with each monomer consisting of 13 subunits, some of which are mitochondrial and some of which are nuclear. COX15 (cytochrome c oxidase assembly protein COX15 homolog) is a 410 amino acid multi-pass mitochondrial membrane protein belonging to the COX15/ctaA family. Existing as two alternatively spliced isoforms, COX15 is predominantly expressed in tissues containing high rates of oxidative phosphorylation including brain, heart and muscle. COX15 defects are the cause of a neurodegenerative disorder known as Leigh syndrome and cytochrome c oxidase deficiency (COX deficiency).