POFUT3 is a protein O-fucosyltransferase that catalyzes O-fucosylation of serine or threonine residues within elastin microfibril interface (EMI) domains of target proteins including MMRN1, MMRN2, and EMID1 1. The enzyme attaches fucose through an O-glycosidic linkage and functions in the endoplasmic reticulum, where it participates in protein folding and secretion of EMI domain-containing proteins 1. POFUT3 represents a recently reclassified protein previously annotated as an alpha-(1,3)-fucosyltransferase; structural and enzymatic evidence now confirms its role as a POFUT 1. The gene may also exhibit alpha-(1,3)-fucosyltransferase activity toward N-glycan substrates, though this activity remains uncertain in vivo 2. O-fucosylation by POFUT3 and related proteins plays critical roles in diverse biological processes and is implicated in various diseases including cancer 3. POFUT3 is associated with multiple disease phenotypes spanning skeletal abnormalities, placental dysfunction, neurological disorders, and metabolic conditions. The precise therapeutic relevance of POFUT3 inhibition or modification remains to be established in clinical applications.