POGLUT1 (protein O-glucosyltransferase 1) is a dual specificity glycosyltransferase that catalyzes the transfer of glucose and xylose to serine residues within the consensus sequence C-X-S-X-P-C in extracellular EGF repeats of proteins including NOTCH receptors, F7, F9, and CRB2 1. As a positive regulator of Notch signaling, POGLUT1 mediates O-glucosylation of NOTCH1, NOTCH2, and NOTCH3, which is critical for myoblast activation and muscle development 2. Loss of POGLUT1 in myogenic progenitors causes reduced proliferation, enhanced differentiation, and impaired muscle repair, demonstrating its essential role in satellite cell maintenance and function 2. Biallelic POGLUT1 mutations cause limb-girdle muscular dystrophy (LGMD-R21), characterized by reduced satellite cell number and impaired myogenic capacity in patient-derived progenitors 23. Heterozygous POGLUT1 mutations also contribute to Dowling-Degos disease, an autosomal dominant genodermatosis characterized by reticulate hyperpigmentation and follicular papules 4. Beyond muscle, POGLUT1 regulates JAG1-mediated signaling in biliary development, suggesting broader roles in tissue differentiation and homeostasis 5.