{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DOPEY2, also known as C21orf5, is an evolutionarily conserved member of the dopey family whose protein product contains highly conserved leucine zipper‐like domains. Studies in humans and model organisms have implicated this gene in key developmental processes. Notably, its expression is enriched in specific brain regions critical for learning and memory, where proper regulation appears essential for normal cortical lamination and neuronal differentiation. Overexpression in Down syndrome is correlated with altered brain morphogenesis and cognitive deficits, suggesting that DOPEY2 dosage imbalance contributes to the neurological features of the syndrome."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its role in neurodevelopment, DOPEY2 has been implicated in intracellular membrane trafficking. It is a component of a conserved MON2–DOPEY complex that participates in the formation and segregation of recycling endosomes and facilitates the endosome-to-Golgi transport of cargos such as Wntless."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, a circular RNA derived from DOPEY2 (circDOPEY2) has been shown to modulate apoptotic signaling and chemosensitivity in esophageal squamous cell carcinoma by acting as a scaffold that promotes the degradation of key RNA‐binding proteins, thereby impacting the translation of antiapoptotic factors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, genetic analyses have identified DOPEY2 as enriched in rare variants in patients with neurodevelopmental and neurodegenerative disorders, further supporting its role as a dosage-sensitive gene whose dysregulation may contribute to disease pathogenesis, including Alzheimer’s disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mohammed Rachidi, Carmela Lopes, Maher Costantine, et al. "}, {"type": "b", "children": [{"type": "t", "text": "C21orf5, a new member of Dopey family involved in morphogenesis, could participate in neurological alterations and mental retardation in Down syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "DNA Res (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/dnares/dsi004"}], "href": "https://doi.org/10.1093/dnares/dsi004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16303751"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16303751"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Carmela Lopes, Zoubida Chettouh, Jean Maurice Delabar, et al. 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