BCKDHA encodes the E1α subunit of the mitochondrial branched-chain α-ketoacid dehydrogenase (BCKDH) complex, which catalyzes the first committed step in branched-chain amino acid (BCAA) catabolism 1. Together with BCKDHB, BCKDHA forms the E1 heterotetrameric complex that decarboxylates ketoacid derivatives of leucine, isoleucine, and valine to generate acyl-CoA and energy 1. The enzyme's activity is regulated through phosphorylation by BCKDK, which inactivates BCKDHA; notably, BCKDK regulates hepatic gluconeogenesis independent of BCKDHA-mediated BCAA catabolism 2. Biallelic BCKDHA mutations cause classic maple syrup urine disease (MSUD) type 1A, a severe inborn error of metabolism characterized by life-threatening neurologic crises and progressive brain injury 1. Gene replacement therapy using dual-function AAV9 vectors has shown therapeutic promise in preclinical models, preventing perinatal death and stabilizing disease biomarkers 1. Beyond MSUD, BCKDHA dysfunction is implicated in metabolic diseases including type 2 diabetes and obesity 3, where elevated circulating BCAAs associate with insulin resistance 3. Additionally, BCKDHA dephosphorylation promotes hepatocellular carcinoma progression 4, while genetic variation in BCKDHA influences heart failure risk and cardiac structure 5.