PIEZO1 is a mechanosensitive cation channel that serves as a crucial mechanotransducer across multiple organ systems 1. The channel functions as a pore-forming subunit of homotrimeric mechanically activated channels that sense mechanical forces and convert them into cellular responses through calcium influx 2. PIEZO1 exhibits rapid inactivation properties, which are essential for proper mechanosensation and whose disruption leads to various pathologies 3. In vascular systems, PIEZO1 acts as a shear-stress sensor promoting endothelial cell organization and regulating angiogenesis through downstream signaling pathways including HIF-1α and VEGF 4. In lymphatic vessels, PIEZO1 serves as an upstream mechanosensor that regulates flow-activated lymphatic expansion through ORAI1-mediated mechanotransduction 5. In cartilage, mechanical overloading activates PIEZO1, leading to calcium influx and GPX4-regulated ferroptosis in chondrocytes, contributing to osteoarthritis progression 67. Clinically, PIEZO1 mutations cause dehydrated hereditary stomatocytosis and lymphatic malformations, while its therapeutic modulation shows promise for treating osteoarthritis and lymphedema 75. The channel's widespread distribution and diverse physiological roles make it an important therapeutic target for mechanopathologies 8.