• UCP2 is highly expressed in glioblastoma and correlates with poor prognosis, establishing it as a promising therapeutic target.
• Genipin, a natural compound, effectively inhibits UCP2 activity, leading to reduced malignant behavior of GBM tumors.
• Genipin induces ferroptosis by downregulating GPX4 and upregulating ACSL4, providing a novel mechanism for GBM treatment.
• The study demonstrates in vivo and in vitro efficacy of genipin, supporting its clinical potential for GBM therapy.