PIEZO1PIEZO2

PIEZO1 and PIEZO2 are genes that encode mechanosensitive, non-selective cation channels belonging to the PIEZO family. The proteins they produce are large, multi-pass transmembrane channels that oligomerize into trimers and respond to mechanical forces by opening to permit the influx of cations, including calcium. These channels are activated by various forms of mechanical stimulation such as stretch, shear stress, pressure, and membrane curvature.

Structurally, PIEZO1 and PIEZO2 are among the largest known ion channel subunits in mammals. Each subunit contributes numerous transmembrane segments, and the functional channels assemble as trimeric complexes embedded in the plasma membrane. The channels are permeable to multiple cations, with calcium entry playing a key role in downstream signaling.

Tissue distribution and physiological roles differ between PIEZO1 and PIEZO2. PIEZO1 is widely expressed, including in endothelial cells, red blood cells, and various epithelial tissues, and it participates in vascular development, blood flow sensing, maintenance of red blood cell volume, and lymphatic function. PIEZO2 is highly expressed in sensory neurons and Merkel cells and is essential for touch discrimination and proprioception, contributing to the sense of limb position and tactile acuity. Both channels contribute to mechanotransduction in sensory pathways and influence reflexes, pain, and motor coordination.

Genetic alterations in PIEZO1 and PIEZO2 have been linked to human disease and altered physiology. Gain-of-function mutations in PIEZO1 cause erythrocyte dehydration disorders and lymphatic anomalies, while loss or dysfunction of PIEZO2 impairs tactile and proprioceptive sensing. Ongoing research seeks to elucidate their regulatory networks and to explore therapeutic strategies targeting mechanosensitive signaling.