IDH3B is a non-catalytic structural subunit of isocitrate dehydrogenase 3 (IDH3), a critical mitochondrial tricarboxylic acid (TCA) cycle enzyme 1. IDH3B facilitates assembly of the heterotetrameric IDH3 complex and is essential for its full catalytic activity in converting isocitrate to α-ketoglutarate while generating NADH for oxidative phosphorylation 2. IDH3B is widely expressed across tissues, with tissue-specific functional roles: it is required for spermiogenesis and male fertility through mitochondrial energy metabolism, but dispensable for retinal viability in mice despite human genetic associations 2. In disease contexts, IDH3B dysfunction links to retinitis pigmentosa 46 3, and reduced IDH3B levels in Alzheimer's disease brains impair oxidative phosphorylation, triggering a pathogenic feedback loop involving lactate accumulation, histone lactylation, and tau hyperphosphorylation 1. IDH3B upregulation has been associated with uterine prolapse risk through altered expression in sacrouterine tissue 4. Additionally, IDH3B participates in metabolic reprogramming in cancer contexts, where it correlates with suppression of glycolysis and promotion of oxidative phosphorylation 5. Recent studies identify IDH3B as a biomarker for thyroid cancer lung metastasis risk 6 and as a therapeutic target in dry eye disease pathways 7.