Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that synchronizes an extensive range of cellular responses throughout various cell types. This regulation takes place through interactions with members of the endothelial differentiation gene (EDG) family, which are plasma membrane-localized G protein-coupled receptors (GPCRs).1 Within the vast sphingolipid family, two important bioactive lipids stand out: ceramide and sphingosine-1-phosphate (S1P). S1P, which is membrane-derived, is generated by the ceramidase-catalyzed conversion of ceramide to sphingosine, subsequently phosphorylation of sphingosine by its kinases (SphK1, and SphK2).2 Five S1P receptors have been recognised and renamed as S1P1 (EDG-1), S1P2 (EDG-5), S1P3 (EDG-3), S1P4 (EDG-6), and S1P5 (EDG-8).These receptors show both overlapping and manifest tissue expression patterns. Their coupling to several G proteins results in diversified signal transduction pathways, which consecutively explain the diverse cellular effects of S1P. S1P functions through S1P1–5 receptors, which are part of the class A GPCR family. This signal occurs in both autocrine as well as paracrine manners. Expression patterns of S1P receptors vary: S1P1–3 receptors are predominantly demonstrated in various cell types, including immune cells, the cardiovascular system, and the central nervous system (CNS). S1P4 is mostly expressed in lymphoid tissues and lungs, while S1P5 is basically found in the CNS, skin, and spleen.5The receptor function and signaling pathway is summarized in Table 1. Among the most studied functions of S1P signalling is the regulation of lymphocyte recirculation and homing. The S1P/S1P1 receptor axis assist the egress of T and B cells from primary and secondary lymphoid tissues without impairing their activation, proliferation, or effector functions.[3], [4] Due to these unique properties, the S1P1 receptor has become a crucial target in autoimmune disease research, particularly in multiple sclerosis (MS).Fig 1.Fig 2.