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The sphingosine‐1‐phosphate (S1P) family of G protein‐coupled receptors (GPCR) regulates essential cellular processes such as proliferation, migration, cytoskeletal organization, adherens junction assembly, and morphogenesis. S1P, a product from the breakdown of sphingomyelin, binds to the five members of this receptor family, S1P₁, S1P₂, S1P₃, S1P₄, and S1P₅, previously referred to as endothelial differentiation gene (EDG)‐1, ‐5, ‐3, ‐6, and ‐8. S1P receptors are widely expressed in different tissues, so it is not surprising that the S1P receptor family regulates many physiological processes, such as vascular maturation, cardiac development, lymphocyte trafficking, and vascular permeability. FTY720, a new S1P receptor agonist, is undergoing clinical trials as an immunosuppressor. Understanding the physiological role of these receptors and the basics of the ligand‐receptor interaction will potentially …