{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CCDC65 encodes a coiled‐coil domain–containing protein that functions as a critical component of the nexin–dynein regulatory complex (N‐DRC), serving as the ortholog of the Chlamydomonas DRC2 (1,4,5). This N‐DRC component is essential for the regulation and coordination of dynein motor activity in motile cilia; its proper assembly ensures the generation of effective, well‐orchestrated ciliary beating. Mutations in CCDC65 have been shown to disrupt the regulatory network—leading to defects in ciliary beat patterns (even in the absence of gross structural abnormalities by transmission electron microscopy)—thereby contributing to the pathophysiology of primary ciliary dyskinesia (PCD) with clinical manifestations such as chronic respiratory infections and infertility (1,3,5,6). In addition, studies indicate that the absence of CCDC65 is associated with the loss of other regulatory proteins (e.g., Gas8), further impairing the dynein–driven microtubule sliding that is necessary for normal ciliary motility (1,4,5,6). Beyond its well‐established role in regulating cilia, recent observations have suggested that CCDC65 may also be involved in processes related to tumorigenesis, although its specific functions in this context remain to be elucidated (2). Collectively, these findings emphasize the importance of CCDC65 in maintaining axonemal integrity and coordinated ciliary motion, with its disruption underlying both ciliopathy phenotypes and possibly contributing to other pathological conditions.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n References:."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Amjad Horani, Steven L Brody, Thomas W Ferkol, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CCDC65 mutation causes primary ciliary dyskinesia with normal ultrastructure and hyperkinetic cilia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0072299"}], "href": "https://doi.org/10.1371/journal.pone.0072299"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23991085"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23991085"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Tongyuan Deng, Peng Shen, Aimin Li, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Zebrafish Ciliopathy Screen Plus Human Mutational Analysis Identifies C21orf59 and CCDC65 Defects as Causing Primary Ciliary Dyskinesia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2013.08.015"}], "href": "https://doi.org/10.1016/j.ajhg.2013.08.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24094744"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24094744"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Raqual Bower, Douglas Tritschler, Kristyn VanderWaal Mills, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DRC2/CCDC65 is a central hub for assembly of the nexin-dynein regulatory complex and other regulators of ciliary and flagellar motility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E17-08-0510"}], "href": "https://doi.org/10.1091/mbc.E17-08-0510"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29167384"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29167384"}]}]}]}