PPM1B (protein phosphatase, Mg2+/Mn2+ dependent 1B) is a serine/threonine phosphatase belonging to the metal-dependent PPM family that functions as a single subunit enzyme binding manganese/magnesium ions in its active center 1. PPM1B exhibits broad substrate specificity, dephosphorylating CDK2, CDK6, PRKAA1, and PRKAA2, and plays critical roles in immune regulation by inhibiting TBK1-mediated antiviral signaling and terminating TNF-mediated NF-κB activation through IKBKB dephosphorylation 1. Mechanistically, PPM1B regulates multiple signaling pathways through targeted dephosphorylation. It dephosphorylates YBX1 at serine 314, modulating PANoptosis and chemoresistance in gastric cancer 2. PPM1B also regulates RIPK3 phosphorylation in necroptosis control 3 and participates in TGF-β pathway activation through BRISC-mediated K63 deubiquitination 4. Additionally, PPM1B forms functional complexes with RBM10 and YBX1 to regulate cancer cell proliferation 5. Clinically, PPM1B dysfunction associates with multiple diseases. Loss-of-function variants in PPM1B are linked to premature ovarian insufficiency through impaired folliculogenesis and ovulation 6. In gastric cancer, PPM1B downregulation promotes tumor growth and cell cycle progression via the TRIM25-mediated degradation pathway 7. PPM1B deubiquitination deficiency contributes to arterial stiffness in metabolic syndrome 4 and USP12-mediated PPM1B regulation affects lung tumor immunotherapy response 8.