EOGT (EGF domain-specific O-linked N-acetylglucosamine transferase) is an endoplasmic reticulum-resident glycosyltransferase that catalyzes the transfer of N-acetylglucosamine from UDP-GlcNAc to serine or threonine residues within EGF-like domains of secreted and membrane proteins 1. Specifically, EOGT modifies the threonine residue positioned between the fifth and sixth conserved cysteines of folded EGF domains 2. This modification is distinct from cytoplasmic O-GlcNAc transferase (OGT), as EOGT operates exclusively in the ER lumen 1. A major substrate of EOGT is Notch receptor, whose 29-36 EGF repeats undergo O-GlcNAc modification to potentiate Delta-like ligand-mediated Notch signaling, thereby regulating vascular development and cell-fate specifications 3, 2. Loss-of-function mutations in EOGT cause Adams-Oliver syndrome, a congenital disorder characterized by abnormal vascular development 1, 3. Beyond developmental roles, EOGT exhibits oncogenic functions. EOGT is upregulated in hepatocellular carcinoma and pancreatic cancer, where it promotes proliferation and migration through Notch pathway activation 4, 5. In HCC, EOGT knockdown enhances ferroptosis sensitivity via the HEY1-SLC7A11 axis and serves as a prognostic biomarker correlating with immune suppression and poor outcomes 4, 6.