PDHB encodes the beta subunit of pyruvate dehydrogenase E1, which heterodimerizes with PDHA1 to form the catalytic E1 component of the pyruvate dehydrogenase (PDH) complex 12. The PDH complex catalyzes thiamine pyrophosphate-dependent conversion of pyruvate to acetyl-CoA and CO2, linking glycolysis to the mitochondrial TCA cycle 2. Beyond canonical metabolism, PDHB regulates skeletal muscle differentiation via the FoxP1-Arih2 axis, with PDHB expression decreased ~50% in aged muscle but increased 3-4 fold during myogenic differentiation; PDHB overexpression improved d-galactose-induced muscle atrophy in mice 3. PDHB is dysregulated in multiple cancers: elevated expression in hepatocellular carcinoma promotes glycolytic reprogramming and sorafenib resistance through transcriptional activation of SLC2A1, GPI, and PKM2 4, while reduced expression in renal cell carcinoma correlates with immunosuppressive microenvironments and poor prognosis 5. PDHB functions as a cuproptosis regulator, with its downregulation suppressing copper-induced cell death in oral squamous cell carcinoma and steroid-induced osteonecrosis 67. Pathogenic PDHB mutations cause autosomal recessive pyruvate dehydrogenase deficiency presenting with neonatal lactic acidosis and neurological dysfunction 8. PDHB expression correlates with immune cell infiltration and immunotherapy response across cancers 9.