This review synthesizes evidence that CNPY2, an ER-luminal regulator of UPR, mitochondrial dynamics, oxidative stress, and apoptosis, has neuroprotective roles in Parkinson's and Huntington's disease and discusses its therapeutic potential across cancer, cardiovascular, and neurodegenerative…

By linking CNPY2 to core Parkinson's-relevant mechanisms—ER stress/proteostasis, mitochondrial dysfunction, and oxidative stress—this paper highlights a tractable molecular target that could inform neuroprotective strategies and biomarker development, though primary mechanistic and in vivo…

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- κ B, AKT/GSK3 β , PI3K/Akt/mTOR and HIF-1 α , promoting epithelial-mesenchymal transition (EMT), tumor survival and metastasis, CNPY2 is also critical in non-cancer conditions. In neurodegenerative disorders including Parkinson's and Huntington's, 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's 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.