{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T11:36:29Z","timestamp":1776684989509,"version":"3.51.2"},"reference-count":96,"publisher":"Shared Science Publishers OG","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"Abstract<\/jats:title>\n \n Canopy homolog protein 2 (CNPY2), an endoplasmic reticulum (ER) luminal protein exhibits broad tissue distribution and regulates cellular homeostasis, including unfolded protein responses (UPR), mitochondrial dynamics, oxidative stress, and apoptosis. Beyond its role in cancer progression through pathways such as NF-\n \n \n \u03ba<\/mml:mi>\n <\/mml:math>\n <\/jats:inline-formula>\n B, AKT\/GSK3\n \n \n \u03b2<\/mml:mi>\n <\/mml:math>\n <\/jats:inline-formula>\n , PI3K\/Akt\/mTOR and HIF-1\n \n \n \u03b1<\/mml:mi>\n <\/mml:math>\n <\/jats:inline-formula>\n , promoting epithelial-mesenchymal transition (EMT), tumor survival and metastasis, CNPY2 is also critical in non-cancer conditions. In neurodegenerative disorders including Parkinson\u2019s and Huntington\u2019s, it exerts neuroprotective role by reducing oxidative stress and mitochondrial dysfunction. In cardiovascular tissues, CNPY2 leads to hypoxia-driven angiogenesis, tissue repair, and ischemia-reperfusion protection. Moreover, recent meta-analyses have linked CNPY2 downregulation with Keratoconus pathogenesis, further highlighting its tissue- specific roles. Hence, this review meticulously dissects CNPY2\u2019s structural characteristics, expression patterns, and biological functions across cancer, cardiovascular disease, inflammation and neurological disorders, emphasizing its role on tumor initiation, microenvironmental stress, and chemoresistance, and evaluating its potential as a therapeutic target.\n <\/jats:p>","DOI":"10.15698\/cst2026.03.316","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T10:37:52Z","timestamp":1776681472000},"page":"19-31","source":"Crossref","is-referenced-by-count":0,"title":["Multifaceted role of CNPY2 beyond ER stress: Disease implications and therapeutic potential"],"prefix":"10.15698","volume":"10","author":[{"given":"Shima","family":"Ebadollahibaruq","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingbin","family":"Meng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Hong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"6394","published-online":{"date-parts":[[2026,3,6]]},"reference":[{"key":"b008e9","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1016\/j.biopha.2018.04.123","article-title":"CNPY2 enhances resistance to apoptosis induced by cisplatin via activation of NF-kappaB pathway in human non-small cell lung cancer","volume":"103","author":"Yu","year":"2018","journal-title":"Biomed Pharmacother"},{"issue":"10","key":"b00968","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1038\/nsb1097-793","article-title":"Saposin fold revealed by 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