PPM1G (protein phosphatase, Mg2+/Mn2+ dependent 1G) is a serine/threonine phosphatase belonging to the PPM/PP2C family that catalyzes dephosphorylation of key regulatory proteins 1. As a metal-dependent enzyme requiring Mg2+ or Mn2+ cofactors, PPM1G regulates diverse cellular processes including cell cycle control, gene expression, DNA damage response, apoptosis, and cell migration 2. Mechanistically, PPM1G functions through substrate-specific dephosphorylation. In triple-negative breast cancer, PPM1G dephosphorylates NDR1 at Thr444, reducing YAP phosphorylation and promoting its nuclear translocation to enhance transcriptional activity 3. In cholangiocarcinoma, PPM1G dephosphorylates TET1, destabilizing the protein and impairing its epigenetic regulation of tumor suppressors 4. PPM1G also negatively regulates innate immunity by dephosphorylating STING and MAVS, though pathogens like KSHV hijack this function for immune evasion 5. Clinically, elevated PPM1G expression is associated with poor prognosis across multiple cancers. High PPM1G correlates with hepatocellular carcinoma occurrence, progression, and chemoresistance in triple-negative breast cancer 23. PPM1G promotes pancreatic cancer autophagy via HMGB1 upregulation 6 and affects immune cell infiltration in lung adenocarcinoma 7. These findings position PPM1G as both a prognostic biomarker and potential therapeutic target across cancer types.