In T cells, which express S1PR1 and S1PR4, and other immune cells, these receptors are crucial checkpoints for cell trafficking.41,42 For example, the S1PR1 system guides T lymphocyte migration along a gradient of S1P, out of the lymph node and into blood circulation.41 The approval of fingolimod (FTY-720), a S1PR1 and S1PR3-5 ligand, by the FDA in 2010 marked a milestone in the treatment of relapsing-remitting multiple sclerosis. Here, S1PR1 is linked to relapsing-remitting multiple sclerosis.