NDUFB10 is an accessory subunit of mitochondrial respiratory chain complex I that plays a critical role in complex I assembly and function. As a component of the membrane arm's PD module, NDUFB10 facilitates the functional assembly of the NADH:ubiquinone oxidoreductase holoenzyme and enables electron transfer from NADH to ubiquinone within the oxidative phosphorylation pathway 1. During mitochondrial import, NDUFB10 interacts with the intermembrane space oxidoreductase CHCHD4 and acquires critical disulfide bonds necessary for efficient accumulation and complex I assembly 1. NDUFB10 loss impairs complex I assembly, reduces supercomplex formation, and decreases mitochondrial membrane potential and respiration capacity 2. Mutations in NDUFB10 cause isolated complex I deficiency with severe clinical manifestations including fatal infantile lactic acidosis and cardiomyopathy 1. Deep intronic variants can also produce disease through cryptic exon activation, disrupting NDUFB10 expression and causing mitochondrial disease 3. Beyond classical mitochondrial disease, emerging evidence indicates NDUFB10 regulates tumor immunotherapy response in lung adenocarcinoma; high NDUFB10 expression correlates with immune desert phenotype and poor immunotherapy outcomes, with NDUFB10 knockdown enhancing anti-tumor immunity 4. Additionally, Mendelian randomization analysis identified NDUFB10 as a Grade 1 causally associated gene in idiopathic pulmonary fibrosis pathogenesis 5, suggesting broader roles in chr16 disease mechanisms.