PPM1L (protein phosphatase, Mg2+/Mn2+ dependent 1L) is a serine/threonine phosphatase belonging to the metal-dependent PP2C phosphatase family 1. As a PP2C family member, PPM1L binds manganese/magnesium ions in its active center and functions as a single subunit enzyme involved in regulating diverse cellular functions 1. PPM1L encodes an endoplasmic reticulum (ER) membrane-targeted phosphatase (PP2Ce) with specific activity toward the inositol-requiring protein-1 (IRE1), a key regulator of ER stress responses 2. Through IRE1 dephosphorylation, PPM1L modulates downstream ER stress signaling, including expression of XBP-1, CHOP, and BiP 2. PPM1L is essential for normal adipocyte maturation, with genetic variation associated with human lipid profiles 2. Dysregulation of PPM1L has been implicated in multiple pathological conditions: obesity and metabolic abnormalities 2, altered folliculogenesis in adiposity 3, and non-small-cell lung cancer, where reduced PPM1L expression correlates with aggressive features including metastasis and higher tumor stages 4. Additionally, PPM1L appears as a potential regulator of phosphorylated MAP2 in schizophrenia pathogenesis 5. These findings position PPM1L as a critical metabolic regulator with significant clinical relevance in metabolic disorders and cancer.