GGCT (gamma-glutamylcyclotransferase) is a key enzyme in glutathione metabolism that catalyzes formation of 5-oxoproline from gamma-glutamyl dipeptides, playing a critical role in glutathione homeostasis 1. Beyond its metabolic function, GGCT induces cytochrome c release from mitochondria, triggering apoptotic pathways 2. In cancer biology, GGCT is significantly upregulated across multiple tumor types including gastric, thyroid, lung, pancreatic, and prostate cancers, where it promotes cell proliferation and migration 34. GGCT functions through multiple oncogenic mechanisms: it activates the MAPK/ERK signaling pathway through interaction with mitochondrial protein MRPL9 4, regulates the STAT3-c-Met-MEK-ERK axis 5, and controls HIF-1α expression to promote aerobic glycolysis 6. In papillary thyroid cancer, GGCT stabilizes CD44 to enhance epithelial-mesenchymal transition and metastasis 7, while inhibiting ferroptosis through p53 suppression via RPS15A stabilization 8. Clinically, GGCT inhibition shows promise as anticancer therapy, with GGCT knockdown suppressing tumor growth and inducing apoptosis 3. Notably, 5-oxoproline supplementation—which inhibits GGCT—simultaneously protects against doxorubicin-induced cardiotoxicity while suppressing tumor proliferation 9, suggesting GGCT as a therapeutic target with potential dual benefits.