EXT2 and glioblastoma: In this study, we have uncovered a novel role of EXT2 in GBM cell therapy response by revealing that (i) EXT2 depletion reduces cell survival and mediates radiosensitization, (ii) EXT2-depleted GBM cells exhibit dysregulated SAM metabolism, particularly in the downregulation of the transsulfuration pathway, and (iii) ferroptosis plays a pivotal role in the radiosensitizing effect of EXT2 depletion.