In the present study, after overexpressing SPNS2 in HCT116 cells, extracellular S1P concentration significantly increased without changing the intracellular S1P concentration, which was consistently with previous finds that SPNS2 does not influence the level of intracellular S1P in SPNS2 deficient mice (49) and ectopic SPNS2 expression didn’t alter intracellular level of S1P in lung cancer cells (16). Here, SPNS2 is linked to lung cancer.