Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite that regulates diverse biologic processes. SGPP2 catalyzes the degradation of S1P.The deduced 399-amino acid protein has a calculated molecular mass of 44.7 kD and shares 39.3% amino acid identity with SGPP1. SGPP2 has an N-terminal hydrophobic region, 3 conserved phosphatase-family motifs, and is predicted to be an integral membrane protein with as many as 9 membrane-spanning segments. Immunofluorescence microscopy showed a reticular staining pattern in the perinuclear and cytosolic regions of HEK293 cells, and SGPP2 colocalized with an endoplasmic reticulum antibody. Northern blot analysis of human tissues detected a 5.1-kb transcript with high expression in kidney and heart, followed by brain, colon, lung, and small intestine.