NDUFAF8 is a mitochondrial assembly factor essential for proper biogenesis of respiratory complex I. It functions as a stabilizer of NDUFAF5 during the early stages of complex I assembly in the mitochondrial matrix 1. Mechanistically, NDUFAF8 acts as a scaffolding protein that facilitates the incorporation of core and accessory subunits into the nascent complex I structure, as evidenced by complexome profiling studies showing stalled assembly intermediates in patient fibroblasts 2. Pathogenic variants in NDUFAF8 cause mitochondrial complex I deficiency with diverse clinical manifestations. Biallelic mutations have been associated with Leigh syndrome, characterized by symmetrical neuroimaging lesions in basal ganglia, thalamus, and brainstem, alongside developmental regression and premature death 23. More recently, NDUFAF8 deficiency has been recognized as a novel genetic cause of autosomal recessive Leber Hereditary Optic Neuropathy (arLHON) with subacute vision loss, broadening the phenotypic spectrum beyond classical Leigh presentation 4. Rare variants have also been tentatively associated with craniofacial anomalies and cardiac defects in complex genetic backgrounds 5. Clinically, NDUFAF8 genetic testing should be considered in patients with unexplained complex I deficiency, particularly those presenting with optic neuropathy or early-onset neurodegeneration, warranting comprehensive genomic screening including intronic sequences for diagnostic completeness 24.