Sphingosine 1-phosphate (S1P) is a bioactive lipid that binds to and activates a family of GPCRs, S1P1-5 (also known as EDG receptors). Interactions between S1P and its receptors mediate cytoskeletal rearrangement and cell migration, with functional consequences in angiogenesis, lymphocyte trafficking, and smooth muscle development (Anliker and Chun, 2004). S1P1 (Edg-1) signals exclusively through Gi, whereas S1P2 (Edg-5) and S1P3 (Edg-3) activate Gi, Gq and G12/13 (Windh et al., 1999). Although S1P1 and S1P3 promote cell migration, S1P2 inhibits cell migration in several cell types; these opposing functions appear to result from differences in the ability of each receptor to activate Gi (Arikawa et al., 2003; Sugimoto et al., 2003; Goparaju et al., 2005). Studies with knockout mice indicate that S1P2 and S1P3 have redundant functions in maintaining vascular integrity during embryonic development (Kono et al., 2004). Cloned human S1P2-expressing cell line is made in the Chem-1 host, which supports high levels of recombinant S1P2 expression on the cell surface for functional detection via the calcium signaling pathway. Thus, the cell line is an ideal tool for screening for agonists, antagonists and modulators at S1P2.