NDUFV3 encodes an accessory subunit of mitochondrial respiratory complex I (NADH:ubiquinone oxidoreductase) that participates in electron transfer from NADH to ubiquinone 1. The gene produces two distinct functional isoforms through alternative splicing: a canonical 10 kDa isoform and a novel 50 kDa isoform, both of which can assemble into mature complex I 23. The longer 50 kDa isoform shows tissue-specific expression patterns, being more abundant in brain tissue compared to heart, liver, kidney, and skeletal muscle 3. This tissue-specific distribution has functional significance, as the brain-specific long isoform affects complex I's susceptibility to redox-dependent flavin mononucleotide (FMN) loss during ischemia/reperfusion conditions, making brain complex I more vulnerable than cardiac complex I 4. NDUFV3 is regulated by splicing factor PTBP1, and its exon skipping contributes to cellular senescence and mitochondrial dysfunction 5. The gene has been identified as a potential therapeutic target for sepsis-related acute respiratory distress syndrome 6 and is involved in β-cell mitochondrial metabolism through miR-29 regulation 7. Located on chromosome 21.3, NDUFV3 may contribute to Down syndrome phenotypes 1.