PLPP2 (phospholipid phosphatase 2) is a magnesium-independent intracellular enzyme that catalyzes dephosphorylation of bioactive lipid mediators including phosphatidate, lysophosphatidate, sphingosine 1-phosphate, and ceramide 1-phosphate 123. Through this phospholipid phosphatase activity, PLPP2 regulates signal transduction and cell cycle progression, particularly G1/S phase transition. PLPP2 dysfunction is implicated in multiple pathologies. In male infertility, RGS14-mediated PLPP2 downregulation impairs spermatogonial stem cell proliferation via suppressed MAPK signaling 4. PLPP2 overexpression correlates with worse prognosis in breast cancer, where it promotes cell proliferation, invasion, and migration through EMT-related pathways affecting CDC34, LSM7, and SGTA expression 5. In lung adenocarcinoma, PLPP2 enhances lipid raft formation and malignant phenotypes 6. PLPP2 is also significantly upregulated in pancreatic ductal adenocarcinoma and represents a potential therapeutic target 7. In neurodegenerative disease, PLPP2 is identified as a key differentially expressed lipid metabolism-related gene in Alzheimer's disease progression 8. Additionally, abnormal PLPP2 upregulation in sphingolipid metabolism may serve as an early biomarker for AD onset, being downregulated during normal aging but upregulated in disease states 9.