SGPL1 and Alzheimer disease: Ceramide, the central metabolite of the sphingolipid pathway, has been implicated in apoptosis, while S1P has been reported to promote cell survival and differentiation.6 - 8 Ceccom et al. observed that downregulation of sphingosine-1-phosphate kinase 1 (SphK1) or upregulation of S1P lyase (SPL) reduced S1P synthesis in AD brains.9