Contradicting conventional understanding, Gasdermin E (GSDME), a known pyroptosis mediator, paradoxically enables glioblastoma cells to resist pyroptotic death while promoting tumor progression. Researchers found that glioblastoma modulates GSDME’s post-translational modifications and localization to disrupt canonical cleavage, thereby subverting inflammatory cell death mechanisms. This dual role offers fresh insights into glioblastoma biology and suggests targets for interventions designed to overcome cell death resistance.