COX18 is a mitochondrial membrane insertase essential for cytochrome c oxidase (Complex IV) assembly and function 1. The protein specifically facilitates translocation of the C-terminal domain of mitochondrially-encoded cytochrome c oxidase subunit II (MT-CO2/COX2) across the mitochondrial inner membrane 1. COX18 functions sequentially after COX20-mediated stabilization of newly synthesized COX2 and before metallochaperone SCO1/SCO2/COA6 action for copper center maturation 1. The protein belongs to the Oxa1/YidC/Alb3 family of membrane protein insertases and shows functional conservation across species 23. COX18 deficiency results in severe isolated Complex IV deficiency and impaired COX assembly 14. Pathogenic biallelic variants in COX18 cause mitochondrial disorders with diverse clinical presentations, including axonal Charcot-Marie-Tooth disease 5, neonatal encephalo-cardio-myopathy with hypertrophic cardiomyopathy, myopathy, and axonal sensory neuropathy 4. COX18 mutations appear rare among patients with isolated COX deficiency, suggesting specific phenotypic associations 6. The gene is tightly regulated with low expression levels, contrasting with constitutively expressed OXA1 2.