Protein O-glucosylation: another essential role of glucose in biology

•Protein O-glucosylation on EGF repeats is essential for Notch signaling.•POGLUT1 recognizes the properly folded EGF repeats and O-gluco sylates the serine within the consensus sequence C1-X-S-X-(P/A)-C2.•XXYLT1 adds a terminal α3-linked Xyl to Xyl-Glc disaccharides on EGF repeats by an SNi-like retaining mechanism.•O-Fuc and O-Glc glycans stabilize EGF repeats, thereby regulating Notch trafficking.