CKAP5, also known as cytoskeleton-associated protein 5, is a conserved microtubule plus tip protein. It plays a crucial role in regulating microtubule-chromosome attachments, spindle assembly, and cytoskeletal crosstalk between microtubules and actin filaments [1,2,4]. It is involved in pathways related to mitosis, meiosis, and cell-cycle progression, and is of great biological importance for processes like chromosome alignment, oocyte maturation, and cell growth [1,2,5]. Genetic models, such as knockout mice, can provide insights into its functions.

Depletion of CKAP5 in human cells impairs CENP-E localization at kinetochores, increases kinetochore-microtubule stability and attachment errors, and reduces CENP-E-BubR1 interaction [1]. In multiple tissue-origin cancer cells, CKAP5 is preferentially essential in aneuploid, chromosomally unstable cells, and sensitivity to its depletion is correlated with that of CENP-E [1]. In human oocytes, CKAP5 is an essential component of the huoMTOC, and disrupting it leads to spindle assembly defects and oocyte maturation arrest [2]. In cancer cells, downregulating CKAP5 increases sensitivity to microtubule-targeting chemotherapeutic drugs [3]. In mice, heterozygous Ckap5 knockout leads to a premature ovarian insufficiency-like phenotype, characterized by reduced primordial follicle pool and accelerated follicular atresia [6].

In conclusion, CKAP5 is vital for regulating microtubule-related functions, spindle assembly, and cytoskeletal crosstalk. Its deficiency in KO mouse models reveals its significance in mitosis, meiosis, and in diseases like premature ovarian insufficiency and genetically unstable cancers, providing potential targets for therapeutic intervention.

References:

1. Lakshmi, R Bhagya, Nayak, Pinaki, Raz, Linoy, Ben-David, Uri, Manna, Tapas K. 2024. CKAP5 stabilizes CENP-E at kinetochores by regulating microtubule-chromosome attachments. In EMBO reports, 25, 1909-1935. doi:10.1038/s44319-024-00106-9. https://pubmed.ncbi.nlm.nih.gov/38424231/

2. Wu, Tianyu, Dong, Jie, Fu, Jing, Sang, Qing, Wang, Lei. 2022. The mechanism of acentrosomal spindle assembly in human oocytes. In Science (New York, N.Y.), 378, eabq7361. doi:10.1126/science.abq7361. https://pubmed.ncbi.nlm.nih.gov/36395215/

3. Rossi, Francesca, Beltran, Manuel, Damizia, Michela, Lavia, Patrizia, Bozzoni, Irene. 2021. Circular RNA ZNF609/CKAP5 mRNA interaction regulates microtubule dynamics and tumorigenicity. In Molecular cell, 82, 75-89.e9. doi:10.1016/j.molcel.2021.11.032. https://pubmed.ncbi.nlm.nih.gov/34942120/

4. Sabo, Jan, Dujava Zdimalova, Michaela, Slater, Paula G, Braun, Marcus, Lansky, Zdenek. 2023. CKAP5 enables formation of persistent actin bundles templated by dynamically instable microtubules. In Current biology : CB, 34, 260-272.e7. doi:10.1016/j.cub.2023.11.031. https://pubmed.ncbi.nlm.nih.gov/38086388/

5. Chatterjee, Sushmita, Naidu, Gonna Somu, Hazan-Halevy, Inbal, Zaidel-Bar, Ronen, Peer, Dan. 2023. Therapeutic gene silencing of CKAP5 leads to lethality in genetically unstable cancer cells. In Science advances, 9, eade4800. doi:10.1126/sciadv.ade4800. https://pubmed.ncbi.nlm.nih.gov/37018392/

6. Hu, Zihao, Gao, Jingping, Long, Panpan, Xiao, Hongmei, Huang, Hualin. 2025. CKAP5 deficiency induces premature ovarian insufficiency. In EBioMedicine, 115, 105718. doi:10.1016/j.ebiom.2025.105718. https://pubmed.ncbi.nlm.nih.gov/40252251/