Dolichyl-diphosphooligosaccharide—protein glycosyltransferase subunit 2 (RPN2)

Dolichyl-diphosphooligosaccharide–protein glycosyltransferase subunit 2 (RPN2) is a type I integral membrane glycoprotein, exclusively found in the rough endoplasmic reticulum, that forms a non-catalytic subunit of the oligosaccharyltransferase complex. RPN2 facilitates the co-translational N-glycosylation of nascent polypeptides by mediating the transfer of high mannose oligosaccharides to asparagine residues, which is essential for proper protein folding, stability, and ER function. Beyond its canonical role in glycoprotein biosynthesis, RPN2 modulates cell surface glycosylation events that influence chemoresistance (e.g., P-glycoprotein trafficking), cell proliferation, tumor invasion, and metabolic reprogramming. Pathologically, RPN2 is upregulated in multiple solid and hematological malignancies, associated with aggressive clinical features, and has been identified as a predictive and prognostic marker for cancer and chemoresistance. Therapeutic targeting or silencing of RPN2 can sensitize resistant tumor cells to chemotherapeutic agents and impede oncogenic pathways, but safety is an issue due to its fundamental role in the N-glycosylation process essential for cell viability

Other names

Dolichyl-diphosphooligosaccharide–protein glycosyltransferase 63 kDa subunitRibophorin IIRibophorin-2RPN-IIRPNIISWP1RIBIIR

Sensitization to chemotherapy: RPN2 silencing inhibits glycosylation and membrane localization of multidrug resistance proteins, restoring drug sensitivity (e.g., docetaxel, cisplatin). Regulation of cancer cell stemness and survival via glycosylation pathways and stabilization of oncoproteins (mutant p53, β-catenin).