Magnesium-independent phospholipid phosphatase of the plasma membrane that catalyzes the dephosphorylation of a variety of glycerolipid and sphingolipid phosphate esters including phosphatidate/PA, lysophosphatidate/LPA, diacylglycerol pyrophosphate/DGPP, sphingosine 1-phosphate/S1P and ceramide 1-phosphate/C1P. Also acts on N-oleoyl ethanolamine phosphate/N-(9Z-octadecenoyl)-ethanolamine phosphate, a potential physiological compound. Has both an extracellular and an intracellular phosphatase activity, allowing the hydrolysis and the cellular uptake of these bioactive lipid mediators from the milieu, regulating signal transduction in different cellular processes. Through the dephosphorylation of extracellular sphingosine-1-phosphate and the regulation of its extra- and intracellular availability, plays a role in vascular homeostasis, regulating endothelial cell migration, adhesion, survival, proliferation and the production of pro-inflammatory cytokines (By similarity). By maintaining the appropriate levels of this lipid in the cerebellum, also ensure its proper development and function (PubMed:21319224). Through its intracellular lipid phosphatase activity may act in early compartments of the secretory pathway, regulating the formation of Golgi to endoplasmic reticulum retrograde transport carriers (By similarity). Independently of this phosphatase activity may also function in the Wnt signaling pathway and the stabilization of beta-catenin/CTNNB1, thereby regulating cell proliferation, migration and differentiation in angiogenesis or yet in tumor growth (PubMed:12925589, PubMed:27125875). Also plays a role in integrin-mediated cell-cell adhesion in angiogenesis (PubMed:16099422). a 1,2-diacyl-sn-glycero-3-phosphate + H2O = a 1,2-diacyl-sn-glycerol + phosphate 1,2-dihexadecanoyl-sn-glycero-3-phosphate + H2O = 1,2-dihexadecanoyl-sn-glycerol + phosphate 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H2O = 1,2-di-(9Z-octadecenoyl)-sn-glycerol + phosphate H2O + monoacyl-sn-glycero-3-phosphate = a monoacylglycerol + phosphate (9Z)-octadecenoyl-sn-glycero-3-phosphate + H2O = (9Z-octadecenoyl)-glycerol + phosphate H2O + sphing-4-enine 1-phosphate = phosphate + sphing-4-enine an N-acylsphing-4-enine 1-phosphate + H2O = an N-acylsphing-4-enine + phosphate H2O + N-(octanoyl)-sphing-4-enine-1-phosphate = N-octanoylsphing-4-enine + phosphate H2O + N-(9Z-octadecenoyl)-ethanolamine phosphate = N-(9Z-octadecenoyl) ethanolamine + phosphate Magnesium-independent phospholipid phosphatase. Insensitive to N-ethylmaleimide. Lipid metabolism; phospholipid metabolism. Forms functional homodimers and homooligomers that are not required for substrate recognition and catalytic activity. Can also form heterooligomers with other PLPP2 and PLPP3. Interacts with CTNND1; negatively regulates the PLPP3-mediated stabilization of beta-catenin/CTNNB1. Cycles between the endoplasmic reticulum and the Golgi. Detected in lung, cerebellum and heart atrium. Display a characteristic dynamic and changing pattern of expression throughout the life cycle of the mouse (PubMed:12925589). Expression during early stages of development is specific of structures where multiple inductive interactions occur such as the limb buds, mammary gland primordia, heart cushions and valves among others (PubMed:19123136). Detected in a few cells of the extra-embryonic ectoderm of 6.5 dpc embryos. By 7.5 dpc, starts to be strongly expressed in the anterior visceral endoderm, as well as in the extra-embryonic membranes. By 8.0 dpc, expression extends to a highly localized region around the node and appears at the tip of the allantois. At 8.5 dpc, predominantly expressed in the allantois, the developing gut, the pericardio-peritoneal canal and somites. In 9.5 dpc embryos, persists in the umbilical cord, and is also found in the chorionic region. In later mid-gestation embryos, present at high levels in the apical ectodermal ridge and mesenchyme of the limb buds, in the peripheral nervous system, cranial nerves, and mammary gland primordia (PubMed:12925589). The integrin-binding motif mediates the binding to integrin alpha-5/beta-1 (ITGA5:ITGB1) and integrin alpha-V/beta-3 (ITGAV:ITGB3) and is required for the function in integrin-mediated cell-cell adhesion. The dityrosine basolateral targeting motif mediates localization to the basolateral membrane in polarized cells. N-glycosylated. Contains high-mannose oligosaccharides. The homozygous knockout of Plpp3 is embryonic lethal (PubMed:12925589, PubMed:17610274, PubMed:19123136). It is characterized by a delay in development, absence of chorioallantoic fusion at the 6 somite stage, allantois compaction, impaired remodeling of the primary capillary plexus of the yolk sac and gastrulation defects with low penetrance. Persistence of open neural tube is also frequently observed (PubMed:12925589, PubMed:19123136). Conditional knockout of Plpp3 in the cerebellum is associated with defects in postnatal cerebellum development, modifications in the cytoarchitecture and arrangement of Bergmann glia with a mild non-progressive motor coordination defect (PubMed:21319224). Conditional knockout of Plpp3 in endothelial cells is associated with vascular leakage and hemorrhage that likely result in insufficient cardiovascular development and the observed embryonic lethality (PubMed:27125875). Conditional knockout of Plpp3 in adipocytes does not affect the development of the adipose tissue. However, mutant homozygous mice display lower accumulation of ceramide and sphingomyelin on high fat or Western diets compared to control animals (PubMed:29889835). Belongs to the PA-phosphatase related phosphoesterase family.