BCKDHB encodes the E1β subunit of the branched-chain α-ketoacid dehydrogenase (BCKD) complex, a mitochondrial multienzyme that catalyzes the first committed step in branched-chain amino acid (BCAA) metabolism 1. BCKDHB forms a heterotetrameric E1 complex with BCKDHA, initiating oxidative decarboxylation of α-ketoacids derived from valine, leucine, and isoleucine, ultimately generating acyl-CoA for energy production 1. The decarboxylation involves lipoylamide cofactor-mediated reductive acylation by the E2 subunit, extracting the acyl group for subsequent catalytic steps 1. Biallelic BCKDHB mutations cause maple syrup urine disease type 1B (MSUD-1B), a severe inborn error of metabolism characterized by life-threatening neurologic crises and progressive brain injury resulting from toxic accumulation of branched-chain amino acids and 2-ketoacids 12. Currently managed only through strict protein-restricted diets or liver transplantation, MSUD-1B presents significant clinical burden 1. Beyond MSUD, BCKDHB expression is post-transcriptionally regulated in cardiac tissue, where proper BCAA metabolism is essential for maintaining mitochondrial function and preventing heart failure 3. Dysregulation of BCKDHB contributes to impaired BCAA homeostasis in diabetic cardiomyopathy and sevoflurane-induced neuronal injury 45. Gene replacement therapy using dual-function AAV vectors successfully restores BCKDHB expression and metabolic function in mouse models, representing a promising therapeutic alternative 16.