RFNG (RFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase) is a glycosyltransferase that modifies O-fucose residues on EGF-like repeats in the extracellular domain of NOTCH receptors 1. The enzyme transfers N-acetylglucosamine (GlcNAc) to O-fucose residues, thereby modulating NOTCH signaling activity 1. RFNG functions hierarchically with other fringe family members, where LUNATIC FRINGE dominates over MANIC or RADICAL FRINGE in NOTCH1 pathway modulation 1. Beyond its canonical role, RFNG exhibits non-enzymatic functions through MAPK-mediated phosphorylation at Ser255, which promotes nuclear translocation and interaction with p53, inhibiting apoptosis and ferroptosis in colorectal cancer cells 2. RFNG expression is elevated in senescent pericytes and differentially affects NOTCH3 CADASIL mutants, contributing to protein accumulation and signaling impairment 3. The gene shows altered expression in various cancers and psychiatric disorders, with increased levels associated with poor prognosis in pancreatic adenocarcinoma 4 and disturbed expression patterns in schizophrenia and bipolar disorder 5. RFNG maps to chromosome 17 and exhibits conserved genomic organization with other fringe family members 6.