Ptprn, encoding protein tyrosine phosphatase receptor type N, lacks protein tyrosine phosphatase activity due to mutations in its intracellular catalytic domains but has acquired new cellular roles in the neuroendocrine system [5]. It is expressed in neuroendocrine cells of the hypothalamus, pituitary gland, pancreas, lung, and intestine, and is involved in regulating intrinsic neuronal excitability, tumor progression, and reproduction-related processes [1,2,3,4,5].

In a knockout mouse model, the knockout of Ptprn in hippocampal granule cells led to augmented NaV1.2-mediated sodium currents and higher intrinsic excitability, increasing seizure susceptibility. Conversely, adeno-associated virus-mediated delivery of Ptprn in the dentate gyrus region decreased intrinsic excitability and reduced seizure susceptibility, indicating its role in regulating seizure susceptibility [1]. In female rats, knockdown of Ptprn-2 (a related polypeptide-encoding gene) regulated levels of puberty-related genes in the hypothalamus, serum reproductive hormones, and the morphology of ovarian and gonadotropin cells, delaying the onset of puberty [4]. In glioma, knockdown of Ptprn reduced cell proliferation and migration, and decreased tumor growth in a mouse xenograft model, while its overexpression had the opposite effects [7]. In lung adenocarcinoma, overexpression of Ptprn promoted cell migration, was related to metastasis, and suppressed NK cell cytotoxicity [6]. In low-grade glioma, Ptprn expression was decreased compared to normal brain tissue, and high expression was associated with better overall survival, also correlating with tumor immune infiltration [2]. Additionally, in glioblastoma, Ptprn was part of a cuproptosis-related prognostic model [3].

In conclusion, Ptprn plays essential roles in regulating intrinsic neuronal excitability, puberty onset, and tumor-related processes such as proliferation, metastasis, and immune infiltration. Gene knockout or knockdown models in mice and rats have significantly contributed to understanding its functions in epilepsy, puberty-related disorders, and various cancers including glioma, glioblastoma, and lung adenocarcinoma.

References:

1. Wang, Yifan, Yang, Hui, Li, Na, Tian, Xin, Huang, Zhuo. 2024. A Novel Ubiquitin Ligase Adaptor PTPRN Suppresses Seizure Susceptibility through Endocytosis of NaV1.2 Sodium Channels. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2400560. doi:10.1002/advs.202400560. https://pubmed.ncbi.nlm.nih.gov/38874331/

2. Li, Peng, Chen, Fanfan, Yao, Chen, Zhang, Bei, Zheng, Zelong. 2022. PTPRN Serves as a Prognostic Biomarker and Correlated with Immune Infiltrates in Low Grade Glioma. In Brain sciences, 12, . doi:10.3390/brainsci12060763. https://pubmed.ncbi.nlm.nih.gov/35741647/

3. Zhang, Bohong, Xie, Lin, Liu, Jiahao, Liu, Anmin, He, Mingliang. 2023. Construction and validation of a cuproptosis-related prognostic model for glioblastoma. In Frontiers in immunology, 14, 1082974. doi:10.3389/fimmu.2023.1082974. https://pubmed.ncbi.nlm.nih.gov/36814929/

4. Kang, Tiezhu, Ye, Jing, Qin, Ping, Wang, Juhua, Fang, Fugui. 2021. Knockdown of Ptprn-2 delays the onset of puberty in female rats. In Theriogenology, 176, 137-148. doi:10.1016/j.theriogenology.2021.09.029. https://pubmed.ncbi.nlm.nih.gov/34607132/

5. Stojilkovic, Stanko S, Sokanovic, Srdjan J, Constantin, Stephanie. 2025. What is known and unknown about the role of neuroendocrine genes Ptprn and Ptprn2. In Frontiers in endocrinology, 16, 1531723. doi:10.3389/fendo.2025.1531723. https://pubmed.ncbi.nlm.nih.gov/39926347/

6. Song, Xinyue, Jiao, Xue, Yan, Han, Zhao, Lin, Wei, Minjie. 2021. Overexpression of PTPRN Promotes Metastasis of Lung Adenocarcinoma and Suppresses NK Cell Cytotoxicity. In Frontiers in cell and developmental biology, 9, 622018. doi:10.3389/fcell.2021.622018. https://pubmed.ncbi.nlm.nih.gov/34150744/

7. Wang, Dong, Tang, Fan, Liu, Xi, Zhuo, Jie, Wang, Bo. 2021. Expression and Tumor-Promoting Effect of Tyrosine Phosphatase Receptor Type N (PTPRN) in Human Glioma. In Frontiers in oncology, 11, 676287. doi:10.3389/fonc.2021.676287. https://pubmed.ncbi.nlm.nih.gov/34557405/