New research reveals a paradoxical function of Gasdermin E (GSDME) in glioblastoma, where it mediates resistance to pyroptosis, an inflammatory cell death pathway, while promoting tumor proliferation and immune evasion. This challenges established paradigms of GSDME as solely a pyroptotic executor, highlighting complex post-translational modifications that inhibit its cleavage and pyroptotic activity. These findings could redefine therapeutic strategies aimed at harnessing pyroptosis to combat aggressive brain tumors.