Lipid phosphate phosphatase (LPP3) and vascular development

Lipid phosphate phosphatases (LPP) are integral membrane proteins with broad substrate specificity that dephosphorylate lipid substrates including phosphatidic acid, lysophosphatidic acid, ceramide 1-phosphate, sphingosine 1-phosphate, and diacylglycerol pyrophosphate. Although the three mammalian enzymes (LPP1-3) demonstrate overlapping catalytic activities and substrate preferences in vitro, the phenotypes of mice with targeted inactivation of the Ppap2 genes encoding the LPP enzymes reveal nonredundant functions. A specific role for LPP3 in vascular development has emerged from studies of mice lacking Ppap2b. A meta-analysis of multiple, large genome-wide association studies identified a single nucleotide polymorphism in PPAP2B as a novel predictor of coronary artery disease. In this review, we will discuss the evidence that links LPP3 to vascular development and disease and evaluate potential molecular mechanisms. This article is part of a Special Issue entitled Advances in Lysophospholipid Research.

► Lipid phosphate phosphatases (LPP) are membrane proteins that dephosphorylate lipids. ► LPP3‐catalyzed dephosphorylation of LPA and S1P renders them receptor inactive. ► A nonredundant role for LPP3 in vasculogenesis was revealed in mice lacking Ppap2b. ► A polymorphism in PPAP2B predicts coronary artery disease. ► LPP3's biologic effects may be due to catalytic or non-catalytic functions.