PLPP1 (phospholipid phosphatase 1) is a plasma membrane-localized, magnesium-independent enzyme that catalyzes the dephosphorylation of various bioactive phospholipids including lysophosphatidic acid (LPA), sphingosine 1-phosphate (S1P), phosphatidate, and ceramide 1-phosphate 1. The enzyme plays critical roles in phospholipid metabolism and cellular signaling by regulating extracellular levels of these lipid mediators through its extracellular phosphatase activity 1. In immune function, PLPP1 is essential for phosphatidylcholine and phosphatidylethanolamine synthesis in CD8+ T cells, with its downregulation by PD-1 signaling leading to ferroptosis-mediated T cell death and impaired antitumor immunity 2. The enzyme demonstrates tissue-specific functions, contributing to decidual macrophage residence during pregnancy through the LPA-autophagy axis 3 and regulating lipid metabolism in adipocytes where its modulation affects lipid droplet accumulation 4. PLPP1 expression changes are associated with various pathological conditions including cancer progression 5, Parkinson's disease 6, and cardiovascular disease 7. As part of the broader LPP family, PLPP1 works alongside LPP2 and LPP3 to maintain lipid phosphate homeostasis, though each family member has distinct physiological roles 8.