PGAM2 (phosphoglycerate mutase 2) is a glycolytic enzyme located on chromosome 7 that catalyzes the interconversion of 3- and 2-phosphoglycerate, essential for glycolysis and energy metabolism in skeletal muscle 1. The enzyme's activity is regulated by posttranslational modifications including sumoylation at conserved lysine residues, which is critical for proper glycolytic and mitochondrial function 2. Mutations in PGAM2 cause glycogen storage disease X (GSDX), characterized by exercise-induced cramps, rhabdomyolysis, and elevated serum creatine kinase, distinguishing it from other glycogen metabolism disorders 3. Beyond its canonical metabolic role, PGAM2 exhibits non-metabolic functions in cancer biology: it promotes enzalutamide resistance in prostate cancer by activating antiapoptotic BCL-xL signaling through interaction with 14-3-3ζ protein, while its expression is transcriptionally regulated by androgen receptor 4. In hepatocellular carcinoma, nuclear PGAM2 expression correlates with improved overall survival, suggesting context-dependent prognostic significance 5. Recent evidence indicates PGAM2 is induced by dapagliflozin through PXR activation, promoting angiogenesis and myocardial repair following infarction 6. Clinically, PGAM2 deficiency presents heterogeneous neuromuscular manifestations requiring careful management and lifestyle adaptation 7.