RPN1 (ribophorin I) is a core subunit of the oligosaccharyl transferase (OST) complex located at the endoplasmic reticulum membrane 1. It catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2)) from dolichol-pyrophosphate to asparagine residues in nascent polypeptides, initiating protein N-glycosylation cotranslationally 1. RPN1 associates with the Sec61 translocon complex, facilitating protein translocation across the ER membrane. Beyond its canonical glycosylation function, RPN1 participates in cellular quality control mechanisms. It serves as a target for UFMylation by the UFL1 ligase brought to the ER surface by DDRGK1, preferentially marking ER sheets for autophagic degradation via ER-phagy, paralleling PINK1-Parkin regulation during mitophagy 2. RPN1 also binds the proteasome subunit RPN11 and interacts with the ubiquitin-independent proteasome regulator MIDN 3. Clinically, RPN1 is aberrantly overexpressed across multiple cancer types and associated with poor prognosis 45. RPN1 amplification is the predominant mutation type, linked to genomic instability and elevated tumor burden 6. RPN1 overexpression promotes immunosuppression by recruiting M2 macrophages while suppressing CD8+ T cell infiltration, reducing immunotherapy responsiveness in several malignancies 6. Additionally, RPN1 and other N-glycosylation machinery are upregulated specifically in brain capillaries of Alzheimer's disease patients 7, suggesting involvement in neurodegenerative disease pathology.