Based on these premises, the aim of this study was to investigate in T98G glioma cells, which are wild type for phosphatase and tensin homolog (PTEN), the physiological switch-off signal of PI3K/AKT, the effect of extracellular S1P on Cer metabolism and traffic, and the effect of S1P on the cytotoxicity induced by treatments that promote Cer accumulation in the ER. Here, PTEN is linked to glioma.