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IFRD1 is a stress-responsive protein that is evolutionarily conserved and required for the cellular regeneration program paligenosis; however, how IFRD1 works in paligenosis is not known. Here we demonstrate that IFRD1 is primarily a cytosolic ribosome-binding protein, specifically binding 80S monosomes that are not actively engaged in translation. Using multiple in vivo and in vitro injury models, including cerulein-induced pancreatitis in mice and tunicamycin-induced ER stress in cell culture, we demonstrate that IFRD1 acts as a ribosome-salvaging factor, preventing ribosomes from degradation. In the absence of IFRD1 during ER stress, non-translating 80S ribosomes were unstable and prone to disassembly and selective degradation. The resulting accumulation of degraded ribosomal subunits overwhelmed cellular autophagic machinery, as evidenced by accumulation of the autophagy-tagging protein p62, even though overall autophagic flux remained unaffected. Ultimately, cells lacking IFRD1 showed reduced mTORC1 activity followed by increased cell death, consistent with patterns observed in cells lacking IFRD1 during paligenosis. Thus, we detail a previously unrecognized cellular function for IFRD1 in stabilizing and preserving the mature ribosome pool during metabolic and translational transitions such as paligenosis.<\/jats:p>","DOI":"10.64898\/2026.05.03.720925","type":"posted-content","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T09:20:14Z","timestamp":1778145614000},"source":"Crossref","is-referenced-by-count":0,"title":["Stress-Responsive Protein IFRD1 Protects Assembled Ribosomes via a Ribosome-Salvaging Mechanism"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4107-9600","authenticated-orcid":false,"given":"Charles J.","family":"Cho","sequence":"first","affiliation":[{"name":"Division of Digestive Diseases, Department of Medicine, Emory University, Atlanta, GA"},{"name":"Graduate Program in Genetics and Molecular Biology, Emory University, Atlanta, GA"},{"name":"Graduate Program in Biochemistry, Cell and Developmental Biology, Emory University, Atlanta, 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