PPAPDC2 contains 6 predicted membrane-spanning domains and 3 conserved lipid phosphate phosphatase motifs. RT-PCR detected expression in both human polymorphonuclear leukocytes and HEK293 cells. Dot-blot analysis of human tissues detected strong expression in pancreas, placenta, spleen, liver, kidney, colon, pituitary gland, and thymus, and moderate to low expression in duodenum, whole brain, stomach, esophagus, lung, testis, and heart. Semiquantitative RT-PCR detected PPAPDC2 expression in PMN leukocytes at 60% of levels in liver.PPAPDC2 activity was optimal at pH 7.0 and 8.0 and was independent of divalent cations. Thin-layer chromatography using C14-labeled substrates showed that PPAPDC2 catalyzed dephosphorylation of PSDP to presqualene monophosphate but not PSMP to presqualene alcohol.