Sphingosine-1-phosphate receptor 5 (S1PR5) (S1PR5)

Sphingosine-1-phosphate receptor 5 (S1PR5) is a G protein-coupled receptor that mediates the effects of the signaling lipid sphingosine-1-phosphate (S1P) [UniProt]. It is uniquely expressed in the central nervous system, primarily on oligodendrocytes, and in the immune system on natural killer (NK) cells [PubMed]. In the CNS, S1PR5 is involved in the regulation of oligodendrocyte precursor cell differentiation and the maintenance of myelin, suggesting a role in neuroprotection and repair [NCBI]. In the periphery, it is essential for the egress of NK cells from the bone marrow and spleen into the blood [PubMed]. Therapeutic targeting of S1PR5, typically alongside S1PR1, is a proven strategy for treating relapsing forms of multiple sclerosis [DrugBank]. Drugs such as siponimod and ozanimod act as functional antagonists by inducing receptor internalization, which modulates the immune response and may provide direct CNS benefits [FDA]. This dual action on both the immune system and the CNS makes S1PR5 a key target for managing neuroinflammatory conditions [PubMed].

Other names

S1P5EDG8Endothelial differentiation gene 8S1P receptor 5Sphingosine 1-phosphate receptor Edg-8

Functional antagonism via agonist-induced receptor internalization and degradation