Dolichyl-diphosphooligosaccharide--protein glycosyltransferase 48 kDa subunit (OST48)

Dolichyl-diphosphooligosaccharide--protein glycosyltransferase 48 kDa subunit (OST48), encoded by the DDOST gene, is an essential non-catalytic component of the oligosaccharyltransferase (OST) complex in the endoplasmic reticulum. The OST complex is responsible for transferring glycans to specific asparagine residues (Asn-X-Ser/Thr) on nascent polypeptides, facilitating protein N-glycosylation—a critical process for protein folding, stability, and trafficking. OST48 is required for the assembly and maximal activity of both major human OST complexes and plays a regulatory role in the glycosylation of extracellular matrix proteins such as lysyl oxidase (LOX). Its deficiency or mutation underlies certain congenital disorders of glycosylation (CDG). Additionally, OST48 functions as a receptor for advanced glycation endproducts (AGER1), linking it to AGE processing and diseases associated with aging and metabolic dysregulation, including diabetes and cardiovascular disease. There is no evidence of common drug interactions or approved therapies that selectively target OST48/DDOST, but inhibitors of glycosylation in research (e.g., tunicamycin) affect its pathway, and genetic variants serve as important biomarkers in CDG diagnosis. Therapeutic manipulation of OST48 carries risks given its widespread role in N-glycosylation.

Other names

DDOSTOST48WBP1OSTKIAA0115Oligosaccharyl transferase 48 kDa subunitAdvanced glycation end-product receptor 1 (AGER1)CDG1ROKSWcl45GATD6Oligosaccharyltransferase subunit 48

Tunicamycin inhibits the initial step in N-glycan biosynthesis, thereby reducing glycosylation of OST substrates. Future therapeutic agents targeting OST48 may aim to modulate glycosylation or AGE-related processing by interfering with OST complex activity.