Nearly all structures in our body experience mechanical forces. At a molecular scale, these forces are detected by ion channels that function as mechanotransducers converting physical forces into electrochemical responses. Here we focus on PIEZOs, a family of mechanically activated ion channels comprising PIEZO1 and PIEZO2. The significance of these channels is highlighted by their roles in touch and pain sensation as well as in cardiovascular and respiratory physiology, among others. Moreover, mutations in PIEZOs cause somatosensory, proprioceptive, and blood disorders. The goal here is to present the diverse physiology and pathophysiology of these unique channels, discuss ongoing research and critical gaps in the field, and explore the pharmaceutical interest in targeting PIEZOs for therapeutic development.

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