PGK1 is a glycolytic enzyme that catalyzes the conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate, producing ATP 1. Beyond its canonical enzymatic role, PGK1 functions as a mitochondrial protein kinase that phosphorylates pyruvate dehydrogenase kinase to suppress oxidative phosphorylation and promote glycolysis 2. PGK1 activity is dynamically regulated by multiple post-translational modifications including O-GlcNAcylation, crotonylation, succinylation, phosphorylation, and arginine methylation, which coordinate glycolytic flux and mitochondrial metabolism 23456. In cancer contexts, enhanced PGK1 modification and activation promote the Warburg effect—increased glycolysis coupled with suppressed TCA cycle activity—supporting tumor growth in glioblastoma, colorectal cancer, breast cancer, and esophageal cancer 24567. Macrophage-derived IL-6 enhances PGK1 phosphorylation to promote aerobic glycolysis and tumorigenesis 5. In non-malignant contexts, PGK1 interacts with androgen receptors to regulate granulosa cell metabolism and ovulation, with pathogenic implications for polycystic ovary syndrome 8. PGK1 modifications serve as prognostic biomarkers across multiple cancer types.