Ranbp9, short for RAN binding protein 9, is a multi-domain scaffolding protein. It is involved in integrating extracellular signaling with intracellular targets. Ranbp9 plays a role in the assembly of the CTLH (C-terminal to lissencephaly-1 homology motif) complex, a multisubunit RING E3 ligase. It organizes subunit assembly and controls the oligomeric state of CTLH complex assemblies [1].

In disease-related research, Ranbp9 has diverse roles. In non-small cell lung cancer (NSCLC), its overexpression is common, and patients with higher levels have worse outcomes with platinum-based drugs. Depletion of Ranbp9 abates ATM activation and its downstream targets, making cells more sensitive to ATR kinase and PARP inhibitors [3]. In colorectal cancer, Ranbp9 overexpression inhibits cell growth and colony formation, while its knockdown promotes these processes, suggesting it serves an inhibitory role in CRC [4]. In laryngeal cancer, circ-Ranbp9 (a circRNA spliced from Ranbp9) is downregulated, and it inhibits the proliferation, migration, and invasion of cancer cells [2]. In polycystic ovary syndrome, circ_RanBP9 is increased, and its silencing inhibits the proliferation and promotes the apoptosis of ovarian granulosa cells [5]. In breast cancer, RanBP9 expression is elevated, associated with poor prognosis, and may regulate cell cycle progression and be linked to tumor purity and immune cell infiltration [6]. In Alzheimer's disease mouse models, RanBP9 overexpression accelerates the loss of dendritic spines and reduces dendritic arbor and spine density [7,8].

In conclusion, Ranbp9 is crucial in the assembly of the CTLH complex and has significant impacts on multiple disease conditions. Research using gene-knockout or other loss-of-function models in these diseases has revealed its role in processes such as cell growth, apoptosis, and synaptic function, providing potential therapeutic targets for NSCLC, CRC, laryngeal cancer, polycystic ovary syndrome, breast cancer, and Alzheimer's disease.

References:

1. van Gen Hassend, Pia Maria, Pottikkadavath, Aparna, Delto, Carolyn, Schönemann, Lars, Schindelin, Hermann. 2023. RanBP9 controls the oligomeric state of CTLH complex assemblies. In The Journal of biological chemistry, 299, 102869. doi:10.1016/j.jbc.2023.102869. https://pubmed.ncbi.nlm.nih.gov/36621627/

2. Wang, Zheng, Gu, Jia, Yan, Aihui, Li, Kai. . Downregulation of circ-RANBP9 in laryngeal cancer and its clinical significance. In Annals of translational medicine, 9, 484. doi:10.21037/atm-21-567. https://pubmed.ncbi.nlm.nih.gov/33850881/

3. Tessari, Anna, Soliman, Shimaa H A, Orlacchio, Arturo, Palmieri, Dario, Coppola, Vincenzo. 2020. RANBP9 as potential therapeutic target in non-small cell lung cancer. In Journal of cancer metastasis and treatment, 6, . doi:10.20517/2394-4722.2020.32. https://pubmed.ncbi.nlm.nih.gov/34778565/

4. Qin, Chunzhi, Zhang, Qin, Wu, Guangbin. 2019. RANBP9 suppresses tumor proliferation in colorectal cancer. In Oncology letters, 17, 4409-4416. doi:10.3892/ol.2019.10134. https://pubmed.ncbi.nlm.nih.gov/30988811/

5. Lu, Xiaohui, Gao, Haijie, Zhu, Bo, Lin, Guilan. . Circular RNA circ_RANBP9 exacerbates polycystic ovary syndrome via microRNA-136-5p/XIAP axis. In Bioengineered, 12, 6748-6758. doi:10.1080/21655979.2021.1964157. https://pubmed.ncbi.nlm.nih.gov/34546853/

6. Meng, Yiling, Ying, Yingxia, Zhang, Meichao, Yao, Yuan, Li, Dong. 2021. A comprehensive bioinformatic analysis of RanBP9 expression and its relation to prognosis in human breast cancer. In Epigenomics, 14, 27-42. doi:10.2217/epi-2021-0464. https://pubmed.ncbi.nlm.nih.gov/34875851/

7. Wang, Ruizhi, Palavicini, Juan Pablo, Wang, Hongjie, Kang, David E, Lakshmana, Madepalli K. 2014. RanBP9 overexpression accelerates loss of dendritic spines in a mouse model of Alzheimer's disease. In Neurobiology of disease, 69, 169-79. doi:10.1016/j.nbd.2014.05.029. https://pubmed.ncbi.nlm.nih.gov/24892886/

8. Wang, H, Lewsadder, M, Dorn, E, Xu, S, Lakshmana, M K. 2014. RanBP9 overexpression reduces dendritic arbor and spine density. In Neuroscience, 265, 253-62. doi:10.1016/j.neuroscience.2014.01.045. https://pubmed.ncbi.nlm.nih.gov/24486966/