NDUFA13 is an accessory subunit of mitochondrial Complex I (NADH dehydrogenase), essential for electron transfer from NADH to ubiquinone in the respiratory chain 1. Unlike catalytic subunits, NDUFA13 functions structurally to stabilize Complex I assembly and integrity 2. Beyond its respiratory role, NDUFA13 participates in interferon/retinoic acid-induced apoptosis and negatively regulates STAT3-mediated transcription 3, with proposed involvement in intestinal immune responses. Biallelic NDUFA13 mutations cause mitochondrial complex I deficiency, nuclear type 28 (OMIM), presenting with severe neurodevelopmental impairment, spasticity, cerebellar ataxia, oculomotor abnormalities, and characteristic bilateral substantia nigra T2 hyperintensities 425. Pathogenic variants reduce Complex I enzymatic activity and protein abundance, impairing mitochondrial respiration and ATP production 26. NDUFA13 also regulates mitochondrial oxidative stress in angiotensin II-induced cardiac remodeling through the SGK3-NLRP3 pathway 7. Recent studies identify NDUFA13 as a prognostic biomarker in multiple myeloma and metabolic dysfunction-associated steatotic liver disease, linking its function to broader metabolic and immune homeostasis 89. Clinical severity correlates with specific mutation types, with missense variants affecting the hydrophilic-membrane arm junction.