FTY720, an immune modulating drug, is effective in various transplant and autoimmune models without inducing a generalized immunosuppressed state. It elicits lymphopenia by causing a reversible redistribution of lymphocytes from circulation to secondary lymphoid tissues. The study demonstrates that FTY720 is phosphorylated by sphingosine kinase, and the phosphorylated form (FTY720-P) acts as a potent agonist at four sphingosine 1-phosphate (S1P) receptors. This suggests that FTY720 functions through S1P signaling pathways to modulate chemotactic responses and lymphocyte trafficking. The findings indicate that FTY720, after phosphorylation, acts as a S1P mimetic, potentially explaining its therapeutic efficacy in multiple sclerosis and other autoimmune disorders. The study also highlights the importance of understanding the metabolic cycle of sphingosine and its derivatives in the immune system.FTY720, an immune modulating drug, is effective in various transplant and autoimmune models without inducing a generalized immunosuppressed state. It elicits lymphopenia by causing a reversible redistribution of lymphocytes from circulation to secondary lymphoid tissues. The study demonstrates that FTY720 is phosphorylated by sphingosine kinase, and the phosphorylated form (FTY720-P) acts as a potent agonist at four sphingosine 1-phosphate (S1P) receptors. This suggests that FTY720 functions through S1P signaling pathways to modulate chemotactic responses and lymphocyte trafficking. The findings indicate that FTY720, after phosphorylation, acts as a S1P mimetic, potentially explaining its therapeutic efficacy in multiple sclerosis and other autoimmune disorders. The study also highlights the importance of understanding the metabolic cycle of sphingosine and its derivatives in the immune system.