NDUFB5 is an accessory subunit of mitochondrial respiratory complex I that plays a critical role in oxidative phosphorylation and cellular energy metabolism. As part of NADH dehydrogenase, NDUFB5 facilitates electron transfer from NADH to ubiquinone, contributing to the mitochondrial respiratory chain 1. The gene shows strong correlations with maximal oxygen uptake (VO2max) and muscle fiber composition, with higher expression associated with better aerobic fitness and increased type 1 muscle fibers 2. NDUFB5 expression increases with exercise training but decreases with aging, particularly in human atrial tissue where downregulation contributes to age-related decline in mitochondrial respiratory capacity 3. Disease relevance includes its identification as a potential biomarker for multiple conditions: septic cardiomyopathy, where it represents one of the most significantly altered hub genes 4, Alzheimer's disease, where downregulation correlates with amyloid-β and tau pathology 5, and ADHD, where altered expression patterns help differentiate patients from controls 6. In diabetic complications, NDUFB5 promotes wound healing through enhanced mitochondrial respiration and cell migration, with its expression regulated by METTL3-mediated m6A modification 1. Additionally, NDUFB5 expression is reduced during epithelial-mesenchymal transition, contributing to metabolic dysfunction 7.