CEP78, a centrosomal protein, is crucial for ciliogenesis, ciliary length control, and centrosome homeostasis [3,6]. It is involved in pathways related to ubiquitination, as it interacts with the EDD1-DYRK2-DDB1VPRBP E3 ubiquitin ligase complex to regulate CP110 levels [3]. CEP78 also has a role in centriole duplication through its interaction with Plk4 [8].

Loss-of-function mutations in CEP78, as shown in knockout mouse models, lead to male infertility, with extremely low sperm count, aberrant sperm morphology, and null sperm motility [1,5]. The infertility cannot be rescued by intracytoplasmic sperm injection treatment [1]. Cep78 knockout mice also exhibit impairments in the retina and outer hair cells of the cochlea [1]. In humans, mutations in CEP78 are associated with cone-rod dystrophy, retinitis pigmentosa, and a distinct type of Usher syndrome, all related to visual and hearing impairments [2,4,7,9].

In conclusion, CEP78 is an essential gene for male fertility, as well as for the normal function of the retina and cochlear outer hair cells. The gene knockout mouse models have been instrumental in revealing its role in these biological processes and associated diseases, highlighting the importance of CEP78 in maintaining normal physiological functions related to cilia-dependent processes in multiple organs [1,2,5].

References:

1. Zhang, Xueguang, Zheng, Rui, Liang, Chen, Yang, Yihong, Shen, Ying. 2022. Loss-of-function mutations in CEP78 cause male infertility in humans and mice. In Science advances, 8, eabn0968. doi:10.1126/sciadv.abn0968. https://pubmed.ncbi.nlm.nih.gov/36206347/

2. Zhu, Tianyu, Zhang, Yuxin, Sheng, Xunlun, Guo, Xuejiang, Zhao, Chen. 2023. Absence of CEP78 causes photoreceptor and sperm flagella impairments in mice and a human individual. In eLife, 12, . doi:10.7554/eLife.76157. https://pubmed.ncbi.nlm.nih.gov/36756949/

3. Gonçalves, André Brás, Hasselbalch, Sarah Kirstine, Joensen, Beinta Biskopstø, Farinelli, Pietro, Pedersen, Lotte Bang. 2021. CEP78 functions downstream of CEP350 to control biogenesis of primary cilia by negatively regulating CP110 levels. In eLife, 10, . doi:10.7554/eLife.63731. https://pubmed.ncbi.nlm.nih.gov/34259627/

4. Lähteenoja, Laura, Häkli, Sanna, Tuupanen, Sari, Rahikkala, Elisa, Falck, Aura. 2022. A novel frameshift variant in CEP78 associated with nonsyndromic retinitis pigmentosa, and a review of CEP78-related phenotypes. In Ophthalmic genetics, 43, 152-158. doi:10.1080/13816810.2022.2045511. https://pubmed.ncbi.nlm.nih.gov/35240912/

5. Liu, Min, Wen, Zongzhuang, Zhao, Dapeng, Gao, Jiangang, Yao, Zhiwei. 2025. Cep78 knockout causes sterility and oligoasthenoteratozoospermia in male mice. In Scientific reports, 15, 63. doi:10.1038/s41598-024-84006-x. https://pubmed.ncbi.nlm.nih.gov/39747485/

6. Hossain, Delowar, Javadi Esfehani, Yalda, Das, Arindam, Tsang, William Y. 2017. Cep78 controls centrosome homeostasis by inhibiting EDD-DYRK2-DDB1VprBP. In EMBO reports, 18, 632-644. doi:10.15252/embr.201642377. https://pubmed.ncbi.nlm.nih.gov/28242748/

7. Fu, Qing, Xu, Mingchu, Chen, Xue, Sui, Ruifang, Chen, Rui. 2016. CEP78 is mutated in a distinct type of Usher syndrome. In Journal of medical genetics, 54, 190-195. doi:10.1136/jmedgenet-2016-104166. https://pubmed.ncbi.nlm.nih.gov/27627988/

8. Brunk, Kathrin, Zhu, Mei, Bärenz, Felix, Antony, Claude, Hoffmann, Ingrid. 2016. Cep78 is a new centriolar protein involved in Plk4-induced centriole overduplication. In Journal of cell science, 129, 2713-8. doi:10.1242/jcs.184093. https://pubmed.ncbi.nlm.nih.gov/27246242/

9. Faruque, Promie R, Hou, Baichun, Oh, Jin Kyun, Tsang, Stephen H. 2024. A Novel CEP78 Variant Presenting as Cone Dystrophy and Hearing Loss. In Ophthalmic surgery, lasers & imaging retina, 55, 742-746. doi:10.3928/23258160-20240717-01. https://pubmed.ncbi.nlm.nih.gov/39172222/