OGDHL (oxoglutarate dehydrogenase L) is a brain-enriched, mitochondrial enzyme that functions as a rate-limiting component of the 2-oxoglutarate dehydrogenase complex (OGDHC), catalyzing the conversion of 2-oxoglutarate to succinyl-CoA in the tricarboxylic acid cycle 1. Beyond its canonical metabolic role, OGDHL exhibits nuclear localization and non-canonical functions including DNA damage induction through CDK4-mediated inhibition of E2F1 signaling, independent of enzymatic activity 2. OGDHL acts as a tumor suppressor in multiple cancer types: its downregulation in hepatocellular carcinoma promotes glutamine metabolic reprogramming, activates mTORC1 signaling, and enhances de novo lipogenesis 3, while in clear cell renal carcinoma, reduced OGDHL expression increases FASN-mediated lipid accumulation and ERK pathway activation 4. In prostate cancer, however, OGDHL loss impairs proliferation and neuroendocrine plasticity 5. OGDHL expression is transcriptionally suppressed by REST in renal fibrosis 6. Biallelic OGDHL variants are associated with neurodevelopmental disorders exhibiting significant phenotypic heterogeneity, including developmental delay, intellectual disability, epilepsy, and corpus callosum dysgenesis, though the gene-disease relationship remains complex 71. OGDHL represents a promising therapeutic target across multiple disease contexts.