POGLUT3 (protein O-glucosyltransferase 3) is a glycosyltransferase that catalyzes O-linked glucose modification of serine residues within extracellular EGF repeats of multiple protein substrates 1. The enzyme transfers glucose from UDP-glucose to serine residues, with a revised consensus sequence of C3-x-x-x-x-x-S-x-x-C4, and can less efficiently transfer xylose 2. POGLUT3 specifically targets EGF repeats in NOTCH1, NOTCH3, fibrillin-1 (FBN1), fibrillin-2 (FBN2), and LTBP1, working cooperatively with POGLUT2 to modify over half of FBN1 EGF repeats 3. These modifications promote secretion of fibrillin and regulate Notch signaling pathway activation by influencing ligand-receptor interactions and cell-surface presentation of Notch proteins 1. POGLUT2/3 double knockout mice exhibit neonatal lethality with reduced fibrillin levels, skeletal defects, and impaired lung development, demonstrating in vivo importance for microfibril assembly and elastic fiber formation 4. Genetically predicted lower POGLUT3 circulating levels associate with reduced prostate cancer and lung adenocarcinoma risk 56, suggesting potential disease relevance beyond fibrillin biology.