Phospholipids and sphingolipids play critical roles in signal transduction, intracellular membrane trafficking, and control of cell growth and survival. We discuss recent progress in the identification and characterization of a family of integral membrane proteins that play central roles in bioactive lipid metabolism and signaling. These five groups of homologous proteins, which are collectively termed Lipid Phosphatases/Phosphotransferases (LPTs), are characterized by a core domain containing six transmembrane spanning α-helices connected by extramembrane loops, two of which interact to form the catalytic site. LPT family members are localized to all major membrane compartments of the cell. The transmembrane topology of these proteins places their active site facing the lumen of endomembrane compartments or the extracellular face of the plasma membrane. Lipid phosphate phosphatases (LPPs) are the best characterized members of the LPT family. By hydrolyzing lysophosphatidic acid (LPA), sphingosine 1-phosphate (S1P) and structurally related substrates, LPPs control intracellular lipid metabolism and regulate cell surface receptor-mediated signaling of S1P and LPA by inactivating these lipids at the plasma membrane. Similarly, other LPT family members, such as sphingomyelin synthases (SMS) and sphingosine phosphate phosphatases (SPP), have been reported to mediate intra- and extra- cellular lipid metabolism with implications in regulation of cell survival and apoptosis. The remaining members of the LPT family, lipid phosphatase related proteins/plasticity related genes (LPR/PRG) and type 2 candidate sphingomyelin synthases (CSS2) are presently much less well studied. These two groups include proteins that lack critical amino acids within the catalytic site and could therefore not use the conserved LPT reaction mechanism to catalyze lipid phosphatase or phosphotransferase reactions. Herein we describe procedures used to analyze the expression and enzymatic activities of LPPs in mammalian and insect cells. Furthermore, we demonstrate that LPR1, a member of the LPR/PRG proteins, despite its enzymatic inactivity, regulates dynamic cell surface protrusions that are identified as filopodia. Analyses of the molecular composition and the mechanistic determinants of these structures reveal that LPR1 regulates filopodia formation in a cdc42 and arp2/3 independent manner. These studies demonstrate a link between the ability of LPTs to interact with phospholipids and influence aspects of cell morphology.