PYGM (glycogen phosphorylase, muscle-associated) is an allosteric enzyme that catalyzes the rate-limiting step of glycogenolysis, the phosphorolytic cleavage of glycogen to glucose-1-phosphate, playing a central role in cellular glucose homeostasis 1. The enzyme is highly expressed in skeletal muscle tissue 2 and functions broadly across tissues 3. Mechanistically, PYGM enhances glycolysis and the pentose phosphate pathway to maintain energy homeostasis 4. Beyond metabolic functions, PYGM exhibits cardioprotective effects by promoting autophagic flux and suppressing thrombospondin-1 expression during myocardial infarction 4, and functions as a metabolic regulator in tumor microenvironments by promoting M2 macrophage polarization in rectal cancer 5. Clinically, PYGM deficiency causes McArdle disease (glycogen storage disease type 5), an autosomal-recessive disorder characterized by exercise intolerance, muscle cramps, and rhabdomyolysis 16. Over 147 pathogenic mutations have been identified, with c.148C>T being most prevalent 1. Exercise-induced symptoms respond to pre-exercise carbohydrate supplementation and low-dose creatine monohydrate 6. Additionally, PYGM was identified as a possible genetic regulator of statin-induced rhabdomyolysis 7, suggesting its role in muscle vulnerability to pharmacological injury.