OGDH encodes the E1 component of the oxoglutarate dehydrogenase complex (OGDHC), a key rate-limiting enzyme in the tricarboxylic acid (TCA) cycle that catalyzes the irreversible decarboxylation of α-ketoglutarate to succinyl-CoA 1. Beyond its classical mitochondrial role in energy metabolism, OGDH functions in both mitochondrial and nuclear compartments 2. In the nucleus, OGDH participates in a nonclassical TCA cycle that generates metabolic intermediates for epigenetic regulation rather than energy production 2. The enzyme's activity is regulated by multiple mechanisms, including direct binding to the co-chaperone TCAIM, which reduces OGDH protein levels and suppresses carbohydrate catabolism 1. OGDH expression is clinically significant in cancer, where reduced OGDH levels promote hepatocellular carcinoma through reprogrammed glutamine metabolism and enhanced lipogenesis 3. In immune contexts, OGDH inhibition improves anti-PD-1 immunotherapy efficacy in melanoma by modulating PD-L1 expression through ATF3-mediated signaling 4. Additionally, OGDH mRNA stability is regulated by m6A methylation during viral infections, where reduced OGDH expression decreases itaconate production and inhibits viral replication 5. The enzyme also contributes to cardiovascular pathology, as the p38α-CREB-OGDH axis regulates succinate production in macrophages, influencing aortic aneurysm development 6.