IDH3G encodes the gamma subunit of mitochondrial isocitrate dehydrogenase (IDH3), a non-catalytic regulatory subunit of the tricarboxylic acid (TCA) cycle enzyme complex. As a regulatory component, IDH3G plays a role in allosteric regulation of isocitrate decarboxylation to alpha-ketoglutarate; the heterotetramer containing IDH3A, IDH3B, and IDH3G subunits requires cooperative function of all components for full enzymatic activity 1. IDH3G is expressed in photoreceptor inner segments and is involved in mitochondrial oxidative metabolism and carbohydrate metabolism 1. IDH3G function is regulated transcriptionally through PGC-1α-mediated mechanisms involving estrogen-related receptor and GA-binding protein-a, which control TCA cycle gene expression in cardiac tissue 2. Lactate-induced histone lactylation upregulates IDH3G expression in lung cancer cells, linking metabolic reprogramming to gene expression 3. Clinically, variants in IDH3G cause X-linked retinitis pigmentosa 99 (RP34), with disease severity typically intermediate and pathogenicity attributed to partial loss of enzymatic activity and mitochondrial function 1. IDH3G is also implicated in HIV-1 pathogenesis, where knockdown increases CD4 levels and reduces viral replication 4, and in gastric cancer drug resistance, where knockdown sensitizes cells to chemotherapy 5.