Sphingosine 1-phosphate (S1P) is a biologically active lysophospholipid that transmits signals through a family of five G-protein-coupled receptors to regulate cell proliferation, migration, cytoskeletal organization, and differentiation (Spiegel and Milstien , 2003). S1P4 receptor was reported to couple to multiple subsets of heterotrimeric G proteins (including Gi/o, and G12/13, and possibly Gs). Unlike other S1P receptors, S1P4 expression is restricted in human and mouse to lymph node, spleen, lung, and thymus (Ishii et al. 2001). This expression pattern suggests potential roles of S1P4 in the immune system. Cloned human S1P4-expressing cell line is made in the Chem-5 host, which supports high levels of recombinant S1P4 expression on the cell surface and contains high levels of the promiscuous G protein to couple the receptor to the calcium signaling pathway. Thus, the cell line is an ideal tool for screening for agonists and antagonists at S1P4.