NDUFA2 encodes an accessory subunit of mitochondrial respiratory chain Complex I (NADH:ubiquinone oxidoreductase), functioning in electron transfer from NADH to ubiquinone within the mitochondrial inner membrane 1. While considered non-catalytic, NDUFA2 is essential for proper Complex I assembly and activity 2. Mutations in NDUFA2 cause mitochondrial Complex I deficiency, manifesting as severe neurological phenotypes including cystic leukoencephalopathy and Leigh syndrome 12. A homozygous splice-site mutation results in exon 2 skipping, leading to reduced Complex I activity, disturbed assembly, and mitochondrial depolarization 2. Beyond primary mitochondrial disorders, NDUFA2 shows broader disease relevance. In myocardial infarction, NDUFA2 downregulation correlates with reduced cardiac function and altered immune infiltration patterns 3. Interestingly, decreased NDUFA2 expression in brain cortex associates with reduced Alzheimer's disease risk and favorable cognitive function, potentially through mitochondrial Complex I modulation 4. The gene also demonstrates prognostic significance in cervical squamous cell carcinoma 5 and shows differential regulation in ovarian cancer drug resistance 6. These findings highlight NDUFA2's critical role in mitochondrial function and its involvement in diverse pathological processes beyond classical mitochondrial diseases.