Tmem63a, a member of the TMEM63 family, functions as a mechanosensitive ion channel. It is involved in processes such as mechanotransduction, with its activity contributing to various physiological functions in different organelles and cell types. It has been associated with pathways related to autophagy and is of significance in understanding normal cellular function and disease mechanisms. Genetic models, especially KO mouse models, have been valuable in studying its functions [2-5, 7-10].

Genetic deletion of Tmem63a in mice led to hypomyelination at postnatal day 14 due to impaired oligodendrocyte precursor cell differentiation, though myelin dysplasia returned to normal levels by P28, indicating its role in early myelin development [3]. In a mouse model of tibial nerve transfer, Tmem63a -/- mice showed decreased mechanical allodynia in the inflammatory and post-amputation state, with reduced macrophage infiltration in the dorsal root ganglion, suggesting its role in chronic post-amputation pain regulation [2]. Loss of Tmem63a and Tmem63b resulted in atelectasis and respiratory failure in mice due to surfactant secretion deficit, highlighting its role in lung function [1].

In conclusion, Tmem63a plays essential roles in multiple biological processes, including myelination, pain regulation, and lung function. Findings from KO mouse models have provided insights into its functions in these processes, contributing to our understanding of related disease areas such as hypomyelination-related disorders, chronic post-amputation pain, and respiratory distress syndromes.

References:

1. Chen, Gui-Lan, Li, Jing-Yi, Chen, Xin, Zhang, Jin, Zeng, Bo. 2024. Mechanosensitive channels TMEM63A and TMEM63B mediate lung inflation-induced surfactant secretion. In The Journal of clinical investigation, 134, . doi:10.1172/JCI174508. https://pubmed.ncbi.nlm.nih.gov/38127458/

2. Pu, Shaofeng, Wu, Yiyang, Tong, Fang, Han, Qingjian, Du, Dongping. 2022. Mechanosensitive Ion Channel TMEM63A Gangs Up with Local Macrophages to Modulate Chronic Post-amputation Pain. In Neuroscience bulletin, 39, 177-193. doi:10.1007/s12264-022-00910-0. https://pubmed.ncbi.nlm.nih.gov/35821338/

3. Wang, Yue-Ying, Wu, Dan, Zhan, Yongkun, Yu, Yongguo, Shi, Yun Stone. 2025. Cation Channel TMEM63A Autonomously Facilitates Oligodendrocyte Differentiation at an Early Stage. In Neuroscience bulletin, 41, 615-632. doi:10.1007/s12264-024-01338-4. https://pubmed.ncbi.nlm.nih.gov/39982638/