PGAM1 (phosphoglycerate mutase 1) is a key glycolytic enzyme that catalyzes the interconversion of 2-phosphoglycerate and 3-phosphoglycerate, representing a crucial metabolic node in cancer cells 1. The enzyme's activity is regulated through multiple post-translational modifications: PKM2 functions as a histidine kinase to phosphorylate PGAM1 at H11 in a PEP-dependent manner, which is essential for enzymatic activity 1. Additionally, Src-mediated phosphorylation at Y119 facilitates PKM2 binding and subsequent H11 phosphorylation 1. HAT1 catalyzes PGAM1 succinylation at K99, further enhancing its enzymatic activity and stimulating glycolytic flux 2. PGAM1 can also utilize fructose-1,6-bisphosphate as a phosphate donor, creating an intrapathway feedback mechanism for glycolysis 3. In cancer, PGAM1 is highly expressed and associated with poor prognosis 4. Its inhibition promotes hepatocellular carcinoma ferroptosis through downregulation of LCN2 and PD-L1, enhancing anti-PD-1 immunotherapy efficacy 4. PGAM1 is also secreted via exosomes in prostate cancer, where it interacts with ACTG1 to promote angiogenesis and metastasis 5. These findings establish PGAM1 as a critical metabolic regulator and potential therapeutic target in cancer.