O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) is a key metabolic enzyme that catalyzes the O-GlcNAcylation of serine and threonine residues on target proteins, functioning as a critical sensor of cellular metabolic status 1. The enzyme operates through hexosamine biosynthetic pathway-dependent mechanisms and can be activated by ROS-induced oxidation at cysteine 845 in its catalytic domain 2. OGT regulates diverse cellular processes including glucose metabolism, nucleotide synthesis, and stress responses through specific protein modifications. Key targets include FOXK2 for ferroptosis resistance, NF-κB p65 for astrocyte activation control, PRPS1 for nucleotide synthesis regulation, and SLC7A11 for cystine transport 2345. Disease relevance is significant in cancer biology, where elevated OGT expression promotes tumorigenesis, metastasis, and chemoresistance through multiple pathways including HIF-1α regulation and metabolic reprogramming 16. The enzyme's stability is regulated by USP8-mediated deubiquitination, and its activity can be enhanced by PI3Kβ-mediated phosphorylation 57. Clinically, OGT levels correlate with cancer prognosis and treatment resistance, making it a promising therapeutic target 86.