{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T08:49:47Z","timestamp":1786870187944,"version":"build-2736575974"},"reference-count":72,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:00:00Z","timestamp":1744156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["R01GM129633"],"award-info":[{"award-number":["R01GM129633"]}]},{"name":"National Institutes of Health","award":["U01AI170018"],"award-info":[{"award-number":["U01AI170018"]}]},{"name":"National Institutes of Health","award":["R35GM118337"],"award-info":[{"award-number":["R35GM118337"]}]},{"name":"National Institutes of Health","award":["R01HL076179"],"award-info":[{"award-number":["R01HL076179"]}]},{"name":"National Institutes of Health","award":["R01AA028947"],"award-info":[{"award-number":["R01AA028947"]}]},{"name":"National Institutes of Health","award":["U01AI186997"],"award-info":[{"award-number":["U01AI186997"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Extracellular cold-inducible RNA-binding protein (eCIRP) is a critical damage-associated molecular pattern (DAMP) that drives inflammation and tissue injury in hemorrhagic and septic shock, and has emerged as a promising therapeutic target. Since then, extensive research using preclinical models of diseases and patient materials has explored eCIRP\u2019s role in driving inflammatory responses and its potential as a biomarker. The main objective of this comprehensive review is to provide a detailed overview of eCIRP, covering its discovery, role in disease pathophysiology, mechanisms of release and action, potential as a biomarker, and therapeutic strategies targeting eCIRP in preclinical models of inflammatory and ischemic diseases. We examine the molecular, cellular, and immunological mechanisms through which eCIRP contributes to disease progression, and explore both well-established and emerging areas of research. Furthermore, we discuss potential therapeutic strategies targeting eCIRP across a broad spectrum of inflammatory conditions, including shock, ischemia\u2013reperfusion injury, neurodegenerative diseases, and radiation injury.<\/jats:p>","DOI":"10.3390\/ijms26083524","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T07:49:02Z","timestamp":1744184942000},"page":"3524","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Extracellular Cold-Inducible RNA-Binding Protein: Progress from Discovery to Present"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8195-4505","authenticated-orcid":false,"given":"Monowar","family":"Aziz","sequence":"first","affiliation":[{"name":"Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA"},{"name":"Departments of Surgery and Molecular Medicine, Zucker School of Medicine, Manhasset, NY 11030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irshad H.","family":"Chaudry","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1557-0394","authenticated-orcid":false,"given":"Ping","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA"},{"name":"Departments of Surgery and Molecular Medicine, Zucker School of Medicine, Manhasset, NY 11030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1002\/JLB.3MIR1118-443R","article-title":"Extracellular CIRP (eCIRP) and inflammation","volume":"106","author":"Aziz","year":"2019","journal-title":"J. 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