PYGB (glycogen phosphorylase B) is the brain-type isoform of glycogen phosphorylase, serving as the rate-limiting enzyme in glycogenolysis that regulates glycogen mobilization and mobilizes stored glycogen as an energy source 1. As an important allosteric enzyme in carbohydrate metabolism 2, PYGB catalyzes glycogen breakdown to release glucose-6-phosphate (G6P) for glycolysis 3. Mechanistically, PYGB activity is regulated by multiple pathways including hypoxia-stimulated activation through phosphoglycerate kinase 1-dependent mechanisms 3 and transcriptional upregulation by androgen receptor binding to the PYGB promoter 4. PYGB expression is elevated across multiple tumor types, with particularly high expression in cholangiocarcinoma, pancreatic cancer, esophageal squamous cell carcinoma, and lung cancer 3546. In cancer contexts, elevated PYGB promotes metabolic reprogramming toward glycolysis and supports tumor cell proliferation, invasion, and metastasis 354. In non-malignant settings, PYGB inhibition ameliorates high glucose-induced cardiomyocyte apoptosis via Akt-HIF-1α pathway activation, suggesting therapeutic potential in type 2 diabetes mellitus 7. PYGB emerges as a promising prognostic biomarker and therapeutic target across diverse diseases 8.