Moreover, it is also tempting to speculate that Cer removal from the ER, as a consequence of an S1P-hyper-activated PI3K/Akt pathway, could also be involved in the refractoriness of glioma cells to Cer-based treatments, in particular those treatments that, in ER, act through Cer biosynthesis stimulation [8,65]. The gene discussed is AKT1; the disease is central nervous system cancer.