PPM1D encodes a protein phosphatase that plays a critical role in DNA damage response and cell cycle regulation. The protein functions primarily as a negative regulator of the p53 pathway by dephosphorylating key residues including Ser-15 of TP53 and Ser-345 of CHEK1, thereby contributing to the relief of p53-dependent cell cycle arrest 12. PPM1D also mediates dephosphorylation and inactivation of MAPK14 3. Clinically, PPM1D mutations are highly significant in cancer biology, particularly in clonal hematopoiesis of indeterminate potential (CHIP), where they account for a substantial portion of mutations alongside other DNA damage repair genes 4. PPM1D mutations drive clonal expansion specifically in response to cytotoxic chemotherapy, with mutated cells showing increased resistance to apoptosis after DNA damage 5. These mutations are strongly correlated with cisplatin exposure and are found in one-fifth of patients with therapy-related acute myeloid leukemia 56. Additionally, PPM1D has been identified as a driver gene in papillary thyroid carcinoma 7 and shows protective effects against ischemic stroke, where gain-of-function mutations are associated with better clinical outcomes 8.