O-GlcNAcylation is critical in human physiology. The dysregulation of O-GlcNAcylation on various intracellular proteins impacts cardiovascular diseases, the immune system, type 2 diabetes, neurodegeneration diseases, and cancers. In the past decade, extracellular O-GlcNAcylation was discovered from the conserved epidermal growth factor-like (EGF) domain in Drosophila and mammals. Extracellular O-GlcNAcylation is catalyzed by EGF domain O-GlcNAc transferase (EOGT) in the endoplasmic reticulum, and, unlike intracellular O-GlcNAcylation, it is further elongated with galactose and sialic acid in the Golgi apparatus. In this review, we retrospect the studies addressing the catalysis of EOGT, the conserved consensus sequence, the impacts of abnormal extracellular O-GlcNAcylation, and the diseases related to EOGT mutation.

O-GlcNAcylation is critical in human physiology. The dysregulation of O-GlcNAcylation on various intracellular proteins impacts cardiovascular diseases, the immune system, type 2 diabetes, neurodegeneration diseases, and cancers. In the past decade, extracellular O-GlcNAcylation was discovered from the conserved epidermal growth factor-like (EGF) domain in Drosophila and mammals. Extracellular O-GlcNAcylation is catalyzed by EGF domain O-GlcNAc transferase (EOGT) in the endoplasmic reticulum, and, unlike intracellular O-GlcNAcylation, it is further elongated with galactose and sialic acid in the Golgi apparatus. In this review, we retrospect the studies addressing the catalysis of EOGT, the conserved consensus sequence, the impacts of abnormal extracellular O-GlcNAcylation, and the diseases related to EOGT mutation.