NDUFA1 is an X-linked accessory subunit of mitochondrial Complex I (NADH:ubiquinone oxidoreductase) that functions in the transfer of electrons from NADH to ubiquinone within the respiratory chain 1. Although not directly involved in catalysis, NDUFA1 is essential for Complex I assembly, stability, and activity 2. The protein localizes to the mitochondrial inner membrane and contains lipid-exposed surfaces critical for stabilizing Complex I structure through interactions with cardiolipin 3. Pathogenic variants in NDUFA1 cause mitochondrial Complex I deficiency, presenting clinically as mitochondrial encephalomyopathy, Leigh syndrome, myoclonic epilepsy, and developmental delay 2. Recent studies identified NDUFA1 as a biomarker for Alzheimer's disease, with reduced protein levels associated with impaired mitochondrial function in the AD hippocampus 4. The p.Gly32Arg variant has been linked to early-onset dementia in multiple families 5. Additionally, NDUFA1 appears in optic atrophy presentations through recessive variants affecting accessory Complex I subunits 6. Beyond inherited mitochondrial disease, elevated NDUFA1 expression associates with poor prognosis in esophageal cancer through PI3K/Akt pathway activation 7. NDUFA1 also mediates ferroptosis resistance through FSP1 interaction; its suppression by IDH1-R132H mutation aggravates cisplatin-induced acute kidney injury 8.