The role of S1P1-mediated signaling in AD remains poorly understood, however, the lower expression of sphingosine kinase-1 (S1P-synthesizing enzyme) together with enhanced expression of S1P lyase (S1P-degrading enzyme) lead to the loss of the S1P endogenous ligand pool early in AD [58,59]. The gene discussed is SPHK1; the disease is Alzheimer disease.