NDUFAF1 (NADH:ubiquinone oxidoreductase complex assembly factor 1) is a mitochondrial assembly factor essential for respiratory complex I biogenesis. As a component of the MCIA complex, NDUFAF1 mediates the nucleation and maturation of complex I, the largest multiprotein enzyme in oxidative phosphorylation 1. Structurally, NDUFAF1 forms a core assembly complex with ACAD9 and ECSIT, locking the central ND3 subunit in an assembly-competent conformation and facilitating sequential incorporation of the 12-subunit proximal proton pump module 23. NDUFAF1 knockdown reduces complex I amount and activity, impairing mitochondrial respiration and increasing glycolytic flux 14. Biallelic NDUFAF1 mutations cause mitochondrial complex I deficiency, nuclear type 11, a severe metabolic disorder with heterogeneous clinical presentations. Disease manifestations include pediatric hypertrophic cardiomyopathy, leukodystrophy with white matter lesions, developmental regression, and peripheral neuropathy 56. Beyond genetic causes, NDUFAF1 expression is downregulated in childhood allergic asthma and K-Ras-induced mitochondrial dysfunction, suggesting its role extends to disease-associated metabolic alterations 74. Clinically, NDUFAF1 and related mitochondrial genes represent emerging biomarkers for metabolic and genetic diseases affecting energy metabolism.