In 1990, S1PR1 was the first member of the S1P receptor family to be cloned from endothelial cells.

[1] Later, S1PR2 and S1PR3 were cloned from rat brain and a human genomic library respectively.

[2][3] Finally, S1P4 and S1PR5 were cloned from in vitro differentiated human dendritic cells and rat cDNA library.

They are expressed in a wide variety of tissues, with each subtype exhibiting a different cell specificity, although they are found at their highest density on leukocytes.

S1PR4 is confined to lymphoid and hematopoietic tissues whereas S1PR5 primarily located in the white matter of the central nervous system (CNS) and spleen.