RFT1 glycolipid translocator homolog (RFT1)

RFT1 glycolipid translocator homolog (RFT1) is a multi-pass endoplasmic reticulum membrane protein that operates as a transporter (flippase), catalyzing the translocation of the lipid-linked oligosaccharide intermediate Man(5)GlcNAc(2)-PP-dolichol from the cytoplasmic to the luminal side of the ER membrane during N-glycosylation of proteins[1][3][5]. This process is critical for the proper assembly and transfer of N-glycan chains to nascent proteins. Mutations in RFT1 cause congenital disorder of glycosylation type In (CDG1N), presenting with neurological and multisystem involvement due to impaired glycan processing[1][4]. The exact mechanistic action of RFT1 was historically debated, but recent in vitro reconstitution studies confirm RFT1 directly catalyzes flipping of the glycan precursor across the ER membrane[3][5]. RFT1 is essential for normal protein N-glycosylation and may also participate in GPI anchor modification, impacting several post-translational modifications and cellular functions[2]. There are currently no approved drugs targeting RFT1.

Other names

Man(5)GlcNAc(2)-PP-dolichol translocation protein RFT1CDG1NSLC76A1Congenital disorder of glycosylation 1N proteinProtein RFT1 homologRFT1-CDGPutative endoplasmic reticulum multispan transmembrane protein

Drugs targeting RFT1 would likely act by restoring or modifying flippase/translocation activity of glycan precursors for correct N-linked glycosylation