Tmem59l, a transmembrane protein, has diverse functions. It is involved in processes such as DNA damage repair, oxidative stress response, and is associated with pathways like epithelial-mesenchymal transition and TGF-β signaling. It plays a role in multiple biological systems, including neurons, pancreatic β-cells, and has implications in cancer development and progression [1,2,3,5].

In glioblastoma, TMEM59L expression is elevated in recurrent tumors, and its high expression is associated with better prognosis, potentially enhancing radiotherapy sensitivity by increasing ROS-induced DNA damage and inhibiting DNA repair [1]. In mouse models, Tmem59l mutants showed an increased frequency of ureter duplications, indicating its role in restricting ureteric outgrowth in the developing kidney [4]. In neurons, overexpression of TMEM59L induced apoptosis, while its down-regulation protected neurons from oxidative stress-induced cell death and improved mouse behaviors related to anxiety, depression, and memory [3].

In conclusion, Tmem59l is a multifunctional gene involved in DNA damage repair, oxidative stress response, and cell death regulation. Mouse models, especially Tmem59l mutants, have revealed its significance in glioblastoma radiotherapy sensitivity, kidney development, and neuronal function. These findings contribute to understanding disease mechanisms and potentially developing targeted therapies in related disease areas.

References:

1. Gao, Dezhi, Wang, Peng, Zhi, Lin, Qiu, Xiaoguang, Liu, Yanwei. . Expression of TMEM59L associated with radiosensitive in glioblastoma. In Journal of radiation research, 64, 833-841. doi:10.1093/jrr/rrad053. https://pubmed.ncbi.nlm.nih.gov/37439405/

2. Shi, Chang, Zhang, Lizhi, Chen, Dan, Guo, Huiqi, Sun, Lei. 2022. Prognostic value of TMEM59L and its genomic and immunological characteristics in cancer. In Frontiers in immunology, 13, 1054157. doi:10.3389/fimmu.2022.1054157. https://pubmed.ncbi.nlm.nih.gov/36618425/

3. Zheng, Qiuyang, Zheng, Xiaoyuan, Zhang, Lishan, Xu, Huaxi, Zhang, Yun-Wu. 2016. The Neuron-Specific Protein TMEM59L Mediates Oxidative Stress-Induced Cell Death. In Molecular neurobiology, 54, 4189-4200. doi:10.1007/s12035-016-9997-9. https://pubmed.ncbi.nlm.nih.gov/27324899/

4. Rutledge, Elisabeth A, McMahon, Andrew P. 2020. Mutational analysis of genes with ureteric progenitor cell-specific expression in branching morphogenesis of the mouse kidney. In Developmental dynamics : an official publication of the American Association of Anatomists, 249, 765-774. doi:10.1002/dvdy.157. https://pubmed.ncbi.nlm.nih.gov/32017326/

5. Kobayashi, Masaki, Yamato, Eiji, Tanabe, Koji, Miyazaki, Satsuki, Miyazaki, Jun-ichi. 2016. Functional Analysis of Novel Candidate Regulators of Insulin Secretion in the MIN6 Mouse Pancreatic β Cell Line. In PloS one, 11, e0151927. doi:10.1371/journal.pone.0151927. https://pubmed.ncbi.nlm.nih.gov/26986842/