SCO2 encodes a mitochondrial copper metallochaperone essential for cytochrome c oxidase (COX) assembly. Working alongside SCO1, SCO2 facilitates copper incorporation into the Cu(A) site of COX subunit II (MT-CO2), a critical step for forming a functional electron transport chain complex. SCO2 may also regulate the redox state of cysteines in SCO1 during maturation of COX subunits. Loss-of-function mutations in SCO2 impair COX assembly and energy production, particularly affecting tissues with high metabolic demand. SCO2 variants cause fatal infantile cardioencephalomyopathy with severe COX deficiency in heart and skeletal muscle 12. SCO2 mutations have also been identified in hereditary motor neuropathies as part of the expanding genetic landscape of rare progressive neuromuscular disease 3. Emerging therapeutic approaches include protein replacement therapy using transduction-domain-mediated delivery of recombinant SCO2 protein or SCO2 mRNA into patient cells, which has shown promise in restoring partial COX activity in patient fibroblasts and animal models 4. Clinical diagnosis of SCO2-related mitochondrial disorders is increasingly facilitated by whole-exome sequencing.