Sphingosine 1-phosphate (S1P) is an active byproduct of sphingomyelin metabolism. Upon secretion, it circulates in the blood via its binding to high-density lipoproteins and albumin. When S1P reaches its target cell it could activate 5 different high affinity receptors belonging to the G-protein coupled receptor superfamily: Sphingosine 1-phosphate receptors, termed S1PR1-5. Stimulation of S1PR receptors triggers a cascade of signaling events depending on the receptor and on the G-protein it couples. Through the different signaling pathways these receptors activate, S1PR receptors are implicated in adherens junction assembly, cytoskeletal changes, cell migration, proliferation and apoptosis.