{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T07:23:57Z","timestamp":1787297037733,"version":"build-2736575974"},"reference-count":92,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Ribophorin I (RPN1), a core component of the oligosaccharyltransferase complex, is traditionally known for its role in endoplasmic reticulum-associated N-glycosylation. Recent studies have identified RPN1 as an emerging regulator of tumor progression and immunity. Aberrant RPN1 overexpression has been reported in multiple malignancies, including glioma, hepatocellular carcinoma, sarcoma, and triple-negative breast cancer, where it is frequently associated with aggressive clinicopathological features and poor prognosis. RPN1 promotes tumor immune evasion by promoting N-glycosylation and stabilization of programmed death-ligand 1 (PD-L1), thereby enhancing immune checkpoint signaling and directly inhibiting anti-tumor T-cell responses. Consequently, elevated RPN1 expression is consistently associated with an immunosuppressive tumor microenvironment rich in M2 macrophages and poor in CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. More importantly, multiple omics signature analyses indicate RPN1 is integrated into several disulfidptosis-related risk models; however, direct experimental evidence confirming the causal linkage between RPN1 and disulfidptosis remains limited. Correlative database data also show potential associations between RPN1 upregulation and genomic instability and treatment resistance. Based on tiered classification of existing evidence (biochemical functional validation vs. multi-omics correlation), this review systematically summarizes the biological roles of RPN1 in cancer, its functions in tumor immunity and disulfidptosis-associated pathways and finally evaluates its potential as a therapeutic target in precision oncology.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1911035","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T06:48:33Z","timestamp":1787294913000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["RPN1 at the crossroads of glycosylation, tumor immunity, and disulfidptosis"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiaoxi","family":"Chang","sequence":"first","affiliation":[{"name":"School of Gongli Hospital Medical Technology, University of Shanghai for Science and Technology","place":["Shanghai, China"]},{"name":"Pudong Gongli Hospital, Shanghai University of Medicine and Health Sciences","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linjun","family":"Weng","sequence":"additional","affiliation":[{"name":"Tongji University Cancer Center, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiquan","family":"Yu","sequence":"additional","affiliation":[{"name":"Pudong Gongli Hospital, Shanghai University of Medicine and Health Sciences","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Shen","sequence":"additional","affiliation":[{"name":"Pudong Gongli Hospital, Shanghai University of Medicine and Health Sciences","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/s41573-021-00371-6","article-title":"PROTAC targeted protein degraders: the past is prologue","volume":"21","author":"B\u00e9k\u00e9s","year":"2022","journal-title":"Nat. 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