PYGB encodes brain-type glycogen phosphorylase, the rate-limiting enzyme of glycogenolysis that mobilizes stored glycogen to provide glucose for cellular energy metabolism. The protein functions as an allosteric enzyme with catalytic and structural properties shared among all known phosphorylases. In cancer contexts, PYGB has emerged as a critical metabolic regulator. Under hypoxic conditions in cholangiocarcinoma, PYGB activity is stimulated in a phosphoglycerate kinase 1-dependent manner, promoting glycogen breakdown and aerobic glycolysis to support tumor progression 1. In pancreatic cancer, PYGB is highly expressed and promotes cell proliferation, invasion, and metastasis through the MAPK/ERK pathway 2. In esophageal squamous cell carcinoma, the androgen receptor directly transactivates PYGB, driving glycolysis and lipid metabolic reprogramming alongside tumor growth 3. In non-small cell lung cancer, PYGB activates both PI3K/AKT and Wnt-β-catenin signaling to enhance proliferation and migration 4 5. Elevated PYGB expression across multiple cancer types correlates with poor prognosis and immune checkpoint elevation 6. Beyond oncology, PYGB inhibition mitigates high glucose-induced cardiomyocyte apoptosis via Akt-HIF-1α activation in a diabetes-relevant model 7. Virtual screening has identified carvedilol, a β-blocker, as a PYGB inhibitor that attenuates cholangiocarcinoma progression 1, positioning PYGB as a dual prognostic biomarker and therapeutic target.