The lipid phosphate phosphatase-related proteins (LPPRs),also known as plasticity-related genes (PRGs),are defined as a novel brain specific subclass of the lipid phosphate phosphatase (LPP) superfamily.LPP proteins are characterized by six-transmembrane domains and function as enzymes dephosphorylating bioactive lipids such as lysophosphatidic acid (LPA).LPPRs,with five members (LPPR-1 to-5) identified so far,share homology with LPPs.However,due to non-conservative mutations in the critical catalytic residues located at the extracellular loops,they are not likely to have a comparable enzy-matic activity to typical LPPs.Members of LPPR family are mainly expressed in central nervous system (CNS),specifically neurons.They showed regulated expression during development and in response to lesion;they induced neurite outgrowth,membrane protrusion,and dendritic spine formation;and are hence considered as regulators of neuronal plasticity and axon regeneration.As a relative newly identified protein family,their functions have just begun to be explored.LPPR-4 (alternatively called PRG-1),the first identified and also the most studied member,was found to facilitate axon growth during develop-ment and regenerative sprouting,and to attenuate neurite collapse induced by LPA.It was also reported to play an important role at the excitatory synapse on glutamatergic neurons,as deletion of LPPR-4 leads to epileptic seizures and increased excit-atory transmission in CA1 pyramidal neurons (Trimbuch et al.,2009).The other four LPPR members were found by in silico analysis,and much less is known compared to LPPR-4.Among them,LPPR-1 and LPPR-5 both have been reported to induce membrane protrusions and neurite outgrowth.LPPR-5 could also impede LPA and axon growth inhibitor Nogo-A induced growth cone collapse and neurite retraction (Strauss and Brauer,2013).Currently,little is known regarding LPPR-2 and LPPR-3.Although characterized by six transmembrane structures,each LPPR member contains a unique C-terminus.Con-sidering LPPR members are all enriched in CNS and are found to have a similar effect on promoting filopodia formation as well as neurite outgrowth,they might play redundant and distinct roles.