ND5 (NADH dehydrogenase subunit 5) is a core subunit of mitochondrial Complex I that catalyzes electron transfer from NADH through the respiratory chain using ubiquinone as an electron acceptor 1. ND5 is essential for Complex I catalytic activity and assembly 1. The gene is subject to post-transcriptional regulation via N1-methyladenosine (m1A) modifications introduced by TRMT10C, which represses ND5 mRNA translation in a tissue-specific and developmentally controlled manner 2. ND5 translation is also regulated by the microprotein SMIM26, which coordinates one-carbon metabolism with Complex I biogenesis 3, and by DAP3, which regulates ND5 expression to modulate mitochondrial respiration 4. ND5 mutations cause severe mitochondrial disease. Pathogenic variants associate with Leigh syndrome, with poorest survival (≤50% at 3 years) observed in MT-ND5 cases 5. The mt-Nd5 A12784G mutation produces vision loss characteristic of Leber's hereditary optic neuropathy in animal models 6. Beyond genetic disease, altered ND5 expression influences cancer biology: in hepatocellular carcinoma, DAP3-mediated ND5 upregulation promotes tumor progression 4, while ND5 reduction in fatty liver exosomes drives breast cancer development through metabolic remodeling 7. Conversely, ND5 mutations in melanoma sensitize tumors to immunotherapy 8, suggesting context-dependent roles in cancer metabolism.