Mechanical force is an essential physical element that contributes to the formation and function of life. The discovery of the evolutionarily conserved PIEZO family, including PIEZO1 and PIEZO2 in mammals, as bona fide mechanically activated cation channels has transformed our understanding of how mechanical forces are sensed and transduced into biological activities. In this Review, I discuss recent structure–function studies that have illustrated how PIEZO1 and PIEZO2 adopt their unique structural design and curvature-based gating dynamics, enabling their function as dedicated mechanotransduction channels with high mechanosensitivity and selective cation conductivity. I also discuss our current understanding of the physiological and pathophysiological roles mediated by PIEZO channels, including PIEZO1-dependent regulation of development and functional homeostasis and PIEZO2-dominated mechanosensation of touch, tactile pain, proprioception and interoception of mechanical states of internal organs. Despite the remarkable progress in PIEZO research, this Review also highlights outstanding questions in the field.

机械力是有助于生命形成和功能的基本物理元素。在哺乳动物中发现进化上保守的 PIEZO 家族，包括 PIEZO1 和 PIEZO2，作为真正的机械激活阳离子通道，改变了我们对机械力如何被感知并转导为生物活动的理解。在这篇综述中，我讨论了最近的结构-功能研究，这些研究说明了 PIEZO1 和 PIEZO2 如何采用其独特的结构设计和基于曲率的门控动力学，使它们能够作为具有高机械敏感性和选择性阳离子电导率的专用机械转导通道。我还讨论了我们目前对 PIEZO 通道介导的生理和病理生理作用的理解，包括 PIEZO1 依赖性的发育和功能稳态调节以及 PIEZO2 主导的触觉机械感觉、触觉疼痛、本体感觉和内部器官机械状态的内感受。尽管 PIEZO 研究取得了显着进展，但本综述也强调了该领域的悬而未决的问题。