Transmembrane proteins with unknown function (TMEMs) as ion channels: electrophysiological properties, structure, and pathophysiological roles

Abstract

A transmembrane (TMEM) protein with an unknown function is a type of membrane-spanning protein expressed in the plasma membrane or the membranes of intracellular organelles. Recently, several TMEM proteins have been identified as functional ion channels. The structures and functions of these proteins have been extensively studied over the last two decades, starting with TMEM16A (ANO1). In this review, we provide a summary of the electrophysiological properties of known TMEM proteins that function as ion channels, such as TMEM175 (K _EL), TMEM206 (PAC), TMEM38 (TRIC), TMEM87A (GolpHCat), TMEM120A (TACAN), TMEM63 (OSCA), TMEM150C (Tentonin3), and TMEM43 (Gapjinc). Additionally, we examine the unique structural features of these channels compared to those of other well-known ion channels. Furthermore, we discuss the diverse physiological roles of these proteins in lysosomal/endosomal/Golgi pH regulation, intracellular Ca ²⁺ regulation, spatial memory, cell migration, adipocyte differentiation, and mechanical pain, as well as their pathophysiological roles in Parkinson’s disease, cancer, osteogenesis imperfecta, infantile hypomyelination, cardiomyopathy, and auditory neuropathy spectrum disorder. This review highlights the potential for the discovery of novel ion channels within the TMEM protein family and the development of new therapeutic targets for related channelopathies.

TMEM channels: potential therapeutic targets for various disorders

Transmembrane proteins (proteins that stretch across the cell membrane) play a role in many cell functions. Yet, we don’t fully understand the structure and roles of many of these proteins. Recent research has found that some transmembrane proteins, like TMEM16A, TMEM87A, TMEM150C, TMEM63, TMEM43, and TMEM175, act as ion channels (pathways for charged particles) crucial for various bodily functions. These proteins participate in normal and abnormal bodily processes, and when they don’t work properly, they can cause diseases like Parkinson’s disease, cancer, brittle bone disease, and hearing loss. By understanding these proteins better, we could develop new treatments for these diseases. Future studies should aim to understand exactly how these proteins work and their potential as targets for treatment. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.