PPM1K is a manganese/magnesium-dependent serine/threonine phosphatase that serves as a central metabolic regulator coordinating branched-chain amino acid (BCAA) catabolism with glucose and lipid metabolism 1. PPM1K forms a functional regulatory pair with BCKDK kinase, controlling the activity of the branched-chain α-ketoacid dehydrogenase (BCKDH) complex by dephosphorylating BCKDHA at Ser-337, thereby activating BCAA catabolism when BCAA levels are elevated 2. Beyond BCAA metabolism, PPM1K regulates lipogenesis by dephosphorylating and inactivating ATP-citrate lyase (ACL) during fasting states 2. Disease relevance includes associations with sarcopenia, where PPM1K deficiency impairs muscle mass and strength through disrupted BCAA catabolism and dysregulated mTOR signaling 3. PPM1K dysfunction also contributes to polycystic ovary syndrome (PCOS), with deficient mice exhibiting hyperandrogenemia and abnormal follicle development that can be ameliorated by dietary BCAA restriction 4. In hepatocellular carcinoma, PPM1K stabilization under glutamine deprivation enhances BCAA catabolism to support nucleotide synthesis and tumor progression 5. PPM1K represents a potential therapeutic target for metabolic diseases, with overexpression improving glucose tolerance and reducing hepatic steatosis in obesity models 2.