B3GLCT encodes a beta-1,3-glucosyltransferase that functions in protein O-linked fucosylation, specifically catalyzing the transfer of glucose from UDP-glucose to O-linked fucose on thrombospondin type-1 repeats (TSRs) 1. This enzyme operates in the endoplasmic reticulum as part of a non-canonical quality control mechanism that recognizes and stabilizes properly folded TSR-containing proteins by glycosylation, thereby promoting their secretion 2. The C-terminal domain contains the active catalytic site, with D421 identified as the catalytic base 3. Loss-of-function mutations in B3GLCT cause Peters-plus syndrome (PPS), a rare autosomal recessive disorder characterized by ocular defects (particularly Peters anomaly with paracentral ring opacity), short stature, brachydactyly, and developmental delay 14. Disease-causing mutations result in complete loss of enzymatic activity and/or protein destabilization 3. Genetic variants in B3GLCT have also been associated with age-related macular degeneration through genome-wide association studies 5. While B3GLCT affects secretion of only a subset of TSR-containing proteins, its loss impacts glycosylation of important extracellular matrix proteins like thrombospondin-1, though secretion may be preserved in some contexts due to compensatory mechanisms involving C-mannosylation 67.