SPHK1 and renal cell carcinoma: SPHK2 seem to be downregulated in RCC tumors (Figure 6B), which goes in line with studies suggesting that although both SPHK1 and SPHK2 use the same physiologic substrate and generate S1P, SPHK2 might have a role opposite to that of SPHK1 as over-expression of SPHK2 suppresses cell growth and enhances apoptosis [61,91].