{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Coiled‐coil domain containing 62 (CCDC62) is emerging as a multifunctional protein with roles in multiple tissues. In prostate cancer cells and prostate stromal cells, CCDC62—also known as ERAP75—acts as a novel coactivator for estrogen receptors. It directly interacts via its conserved LXXLL motif with the ligand‐binding domain of estrogen receptor β (and α), thereby facilitating hormone‐dependent recruitment to estrogen response elements and enhancing transcription of target genes such as cyclin D1, which in turn promotes cell proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the male reproductive system, CCDC62 is highly expressed in the testis, where it is predominantly localized in the cytoplasm of developing spermatids and specifically concentrates at the acrosome in mature sperm. Genetic disruption of Ccdc62 in mice results in a truncated protein and defective acrosome formation, leading to deformed sperm and male infertility, thereby underscoring its critical role in spermiogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its functions in reproductive tissues, a series of genetic studies have implicated CCDC62—as part of the CCDC62/HIP1R locus—in the pathogenesis of Parkinson’s disease (PD). Several genome‐wide association investigations have found that polymorphisms in this region (notably the rs12817488 variant) are associated with altered PD risk, with differences in expression levels observed across patient subgroups and apparent interactions with estrogen‐related pathways. Moreover, psychotropic agents such as fluoxetine have been shown to upregulate CCDC62 transcription, suggesting that modulation of its expression might influence PD‐relevant pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, these findings position CCDC62 as a protein that not only modulates estrogen receptor‐mediated gene transcription critical for prostate cellular functions and proper spermiogenesis, but also contributes to the genetic architecture of PD. Its pleiotropic roles, affected by variations in its coding sequence and transcriptional regulation, highlight CCDC62 as a potential target for therapeutic intervention in both reproductive disorders and neurodegeneration.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ming Chen, Jing Ni, Hong-Chiang Chang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CCDC62/ERAP75 functions as a coactivator to enhance estrogen receptor beta-mediated transactivation and target gene expression in prostate cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Carcinogenesis (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/carcin/bgn288"}], "href": "https://doi.org/10.1093/carcin/bgn288"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19126643"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19126643"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ming Chen, Jing Ni, Yong Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ERAP75 functions as a coactivator to enhance estrogen receptor alpha transactivation in prostate stromal cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Prostate (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/pros.20774"}], "href": "https://doi.org/10.1002/pros.20774"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18563714"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18563714"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yuchi Li, Cailing Li, Shouren Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A nonsense mutation in Ccdc62 gene is responsible for spermiogenesis defects and male infertility in repro29/repro29 mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Reprod (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1095/biolreprod.116.141408"}], "href": "https://doi.org/10.1095/biolreprod.116.141408"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28339613"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28339613"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Nan-Nan Li, Eng-King Tan, Xue-Li Chang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic association study between STK39 and CCDC62/HIP1R and Parkinson's disease."}]}, {"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.0079211"}], "href": "https://doi.org/10.1371/journal.pone.0079211"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24312176"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24312176"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ri-li Yu, Ji-feng Guo, Ya-qin Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The single nucleotide polymorphism Rs12817488 is associated with Parkinson's disease in the Chinese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Neurosci (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jocn.2014.11.024"}], "href": "https://doi.org/10.1016/j.jocn.2014.11.024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25818163"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25818163"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Rong-Rong Liu, Li-Li Zhou, Xing Cheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CCDC62 variant rs12817488 is associated with the risk of Parkinson's disease in a Han Chinese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Neurol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000354333"}], "href": "https://doi.org/10.1159/000354333"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24335092"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24335092"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yanjun Lu, Lu Tan, Na Shen, et al. 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