Sphingosine kinase (SphK or SphK1) is a key enzyme catalyzing the phosphorylation of sphingosine to form sphingosine 1-phosphate (SPP or S1P). Competitive inhibitors of SphK1 block formation of SPP and selectively inhibit cellular proliferation induced by a variety of factors. One potent inhibitor of SphK1 activity is DMS (N,N-dimethylsphingosine). SPP/SphK1 has been implicated as a signaling pathway that regulates diverse cellular functions, including cell growth, proliferation and survival. Specifically, SphK1 is involved in the signaling pathway (s) that protects human hepatocytes from the apoptotic action of TNFα. Furthermore, SPP/SphK1 may play an important role in neuronal survival by regulating activation of SAPKs and caspases. SphK1 is widely expressed with highest levels in adult liver, kidney, heart and skeletal muscle; however, activation of SphK1 disengages cells from their liver-specific phenotype.