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Dysregulation of RPS3 contributes to diverse human disorders, including cancer, inflammatory diseases, neurodegeneration, and resistance to antimicrobial and anticancer therapies. As a cofactor of NF-\u03baB and a participant in DNA damage responses, RPS3 occupies a node that integrates stress signaling with transcriptional reprogramming, enabling both protective and pathological outcomes. The present review critically evaluates mechanistic insights into RPS3 biology, emphasizing recent findings that delineate its context-dependent effects, discrepancies across models, and remaining gaps that restrict translational applications. Understanding these complexities is essential to assess RPS3\u2032s potential as a biomarker and therapeutic target.<\/jats:p>","DOI":"10.1042\/bsr20260051","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T05:55:36Z","timestamp":1788328536000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ribosomal protein S3: a critical regulator of human disease mechanisms"],"prefix":"10.1042","volume":"46","author":[{"given":"Joeline","family":"Dreik","sequence":"first","affiliation":[{"name":"Department of Biology, Faculty of Arts and Sciences, University of Balamand, Tripoli, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa","family":"Al\u00a0Ali","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Arts and Sciences, University of Balamand, Tripoli, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jalil","family":"Daher","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Arts and Sciences, University of Balamand, Tripoli, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4369-5936","authenticated-orcid":false,"given":"Zeina","family":"Nasr","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Arts and Sciences, University of Balamand, Tripoli, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"2026090201553371400_B1","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.bbrc.2008.12.083","article-title":"Emerging functions of ribosomal proteins in gene-specific transcription and translation","volume":"379","author":"Lindstr\u00f6m","year":"2009","journal-title":"Biochem. 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