In summary, findings presented in this report support the concept that the stimulation of autophagy-mediated cancer cell death by THC relies on a modification of the sphingolipid composition of the endoplasmic reticulum of glioma cells that is transmitted to autophagosomes and autolysosomes thereby leading to lysosomal membrane permeabilization, cathepsin release and the subsequent activation of apoptotic cell death. Here, CTSS is linked to cancer.