PLPP2 is a magnesium-independent phospholipid phosphatase that catalyzes dephosphorylation of bioactive lipid mediators including phosphatidate, lysophosphatidate, sphingosine 1-phosphate, and ceramide 1-phosphate, functioning primarily within intracellular compartments. Through modulation of these signaling lipids, PLPP2 regulates cellular processes including cell cycle progression and lipid raft formation. In early-stage lung adenocarcinoma, elevated PLPP2 expression promotes cell proliferation by enhancing lipid raft synthesis, and serves as an independent prognostic risk factor 1. PLPP2 is similarly overexpressed in breast cancer, particularly in ER+ subtypes, where it drives proliferation, invasion, and migration through epithelial-mesenchymal transition pathways 2. Recent evidence suggests PLPP2 functions as a therapeutic target in gastric cancer, where the natural compound 19-hydroxybufalin exerts anticancer activity by binding to PLPP2 and remodeling metabolic networks 3. In pancreatic ductal adenocarcinoma, elevated PLPP2 expression in epithelial cancer cells is associated with the lysophosphatidate-signaling axis, positioning PLPP2 inhibition as a potential therapeutic strategy 4. Additionally, PLPP2 dysregulation contributes to male infertility, as downregulation in spermatogonial stem cells impairs proliferation through reduced MAPK signaling 5, and upregulation correlates with Alzheimer's disease progression in brain tissue 6.