BDH1 (3-hydroxybutyrate dehydrogenase 1) is a mitochondrial matrix oxidoreductase that catalyzes the final step of ketone body metabolism, converting β-hydroxybutyrate to acetoacetate 1. As the rate-limiting enzyme in ketone catabolism, BDH1 functions as a critical metabolic checkpoint in energy homeostasis 1. Mechanistically, BDH1-mediated ketone metabolism activates protective cellular pathways including NRF2-dependent antioxidative signaling 1 and epigenetic modifications that suppress pro-inflammatory genes 2. In T cells, BDH1 promotes β-hydroxybutyrate production, which inhibits interferon regulatory factor 4 (IRF4), suppressing CD8+ T cell activation 3. Additionally, BDH1 coordinates metabolic flux through the acetoacetate-succinate-fumarate pathway to enhance mitochondrial function 1. BDH1 expression is significantly downregulated in diabetic complications including diabetic cardiomyopathy, diabetic kidney disease, and metabolic dysfunction-associated steatohepatitis 412. BDH1 overexpression ameliorates these conditions by reducing oxidative stress, mitochondrial dysfunction, apoptosis, and inflammation 125. BDH1 is also required for beige adipocyte differentiation and metabolic remodeling in response to cold exposure 6. Clinically, enhancing BDH1 activity through SGLT2 inhibitors or gene therapy represents a promising therapeutic strategy for metabolic diseases 431. Genetic duplication of BDH1 associates with neurodevelopmental and cardiac phenotypes 7.