Tmem63a, or transmembrane protein 63A, functions as a mechanosensitive ion channel. It is involved in multiple biological processes, including lysosomal mechanosensing, surfactant secretion in the lungs, and is linked to pathways related to autophagy in triple-negative breast cancer progression. Its study using genetic models, such as KO mouse models, is crucial for understanding its functions [1,2,3,4].

In Tmem63a knockout mice, genetic deletion led to hypomyelination at postnatal day 14 due to impaired oligodendrocyte precursor cell differentiation, though myelin dysplasia returned to normal by P28, indicating TMEM63A-mediated Ca2+ influx is critical for early myelin development [5]. Loss of Tmem63a and Tmem63b in mice resulted in atelectasis and respiratory failure from surfactant secretion deficit, highlighting its role in lung inflation-induced surfactant secretion [3]. Tmem63a -/- mice also showed reduced mechanical allodynia in inflammatory and post-amputation states, with decreased macrophage infiltration in the dorsal root ganglion, suggesting its role in chronic post-amputation pain regulation [6].

In conclusion, Tmem63a is essential for lysosomal mechanosensing, lung surfactant secretion, oligodendrocyte differentiation, and pain regulation. Studies using KO mouse models have revealed its significance in conditions like hypomyelination, respiratory failure, and chronic post-amputation pain, providing insights into disease mechanisms and potential therapeutic targets.