ND1 (mitochondrially encoded NADH dehydrogenase 1) encodes the largest mitochondrially-encoded core subunit of Complex I in the mitochondrial respiratory chain 1. As a vital component of Complex I, ND1 catalyzes electron transfer from NADH through the respiratory chain using ubiquinone as an electron acceptor, playing an essential role in oxidative phosphorylation and ATP synthesis 2. The protein is crucial for both the catalytic activity and proper assembly of Complex I 3. ND1 dysfunction significantly impacts mitochondrial bioenergetics, with mutations leading to impaired Complex I functionality and overall mitochondrial energy production 2. Clinically, ND1 mutations are associated with several serious conditions including Leber hereditary optic neuropathy, where specific mutations like m.3460 G>A cause progressive retinal ganglion cell loss and optic nerve degeneration 34. The gene is also implicated in diabetic cardiomyopathy, where its downregulation contributes to cardiac dysfunction through disrupted mitochondrial genome regulation 2. Additionally, ND1 alterations are widely detected in various cancers and may serve as biomarkers for diagnosis and prognosis 15. Gene therapy approaches using mitochondrially-targeted vectors have shown promise in restoring ND1 function and protecting against disease progression 3.