SMPD2 and cancer: Specifically, we found that RA, when channeled through RARα in RA-sensitive cancer cells, concertedly upregulates on one hand nSMase, thus leading to accumulation of CER, the antiproliferative and proapoptotic sphingolipid, and on the other hand downregulates SK1, pivotal for the synthesis of the oncogenic S1P, the prosurvival sphingolipid.