Piezo-type mechanosensitive ion channel component 1 is a protein that in humans is encoded by the PIEZO1 gene. PIEZO1 is a large mechanosensitive ion channel protein that forms a homotrimeric complex with a distinctive three-bladed, propeller-shaped architecture. Each subunit of PIEZO1 contains between 30 and 40 transmembrane domains. The protein consists of a central pore module and peripheral mechanotransduction modules. The pore module is composed of the last two transmembrane helices, an extracellular cap domain, and an intracellular C-terminal domain.

PIEZO1 functions as a non-selective cation channel capable of conducting both monovalent and divalent cations, including Na⁺, K⁺, and Ca²⁺. The mechanosensitivity of PIEZO1 is a defining characteristic. It can be directly activated by membrane tension, with the peripheral blade and beam structures likely acting as mechanotransduction modules. Notably, PIEZO1 requires lower tension for activation compared to bacterial mechanosensitive channels. The protein exhibits voltage-dependent inactivation. PIEZO1 serves as a mechanotransducer in various cell types and tissues playing roles in processes such as vascular development, red blood cell volume regulation, and epithelial homeostasis.

Piezo1 and its close homolog Piezo2 were cloned in 2010, using an siRNA-based screen for mechanosensitive ion channels.

Piezo1 (this gene) and Piezo2 share 47% identity with each other and they have no similarity to any other protein, making them unique among ion channels. They are predicted to have 24-36 transmembrane domains, depending on the prediction algorithm used. In the original publication the authors were careful not to call the piezo proteins ion channels, but a more recent study by the same lab convincingly demonstrated that indeed Piezo1 is the pore-forming subunit of a mechanosensitive channel. This new "Piezo" family is catalogued as InterPro: IPR027272 and TCDB 1.A.75. Piezo1 homologues are found in C. elegans and Drosophila, which, like other invertebrates, have a single Piezo protein.

It is known (PDB: 6B3R​) that Piezo1 channel is a three-bladed propeller-like structure, or trimer, with unique membrane curvature. When activated, a lever-like mechanogating mechanism is assumed for the flexible blades, opening the central pore to allow for the influx of calcium ions. Typically, this is in response to mechanical tension and ultimately leads to the triggering of downstream signaling pathways. As such, Piezo1 activation is essential to transduction of biochemical signals.

Mechanotransduction refers to cellular responses that arise from the conversion of mechanical stimuli. Piezo1 plays a critical role in maintaining cell volume, especially under osmotic stress. It senses membrane stretches after swelling due to hypotonic conditions and mediates calcium-dependent activation of volume-regulated anion channels (VRACs) and Kca channels, initiating a process known as regulatory volume decrease (RVD) to help cells recover their original size. Potassium and chloride ions are expelled in this process to restore osmotic balance, creating a gradient that encourages water to move out of the cell. This prevents cellular damage from prolonged swelling and is particularly important for cellular homeostasis, as Piezo1 modulates the ionic efflux and water movement. This mechanism is highlighted in erythrocytes, where volume changes in narrow capillaries can lead to hemolysis. Piezo1 activation supports the structural integrity and adaptation of these cells to maintain efficient oxygen transport.

The influx of calcium ions induces changes in membrane potential and intracellular ion concentration, leading to a cascade of signaling pathways. These activate calcium-dependent kinases and cascades like the ERK1/2 branch of the mitogen-activated protein kinase (MAPK) pathway. The MAPK pathway is well characterized and plays a role in regulating a variety of cellular processes. In the ERK1/2 branch, Piezo1-mediated calcium influx phosphorylates downstream targets, regulating gene expression and cell cycle progression, especially in periodontal ligament cells (PDLCs) where tissue remodeling is prominent.

In dorsal root ganglia (DRG), Piezo1 enables cells to detect substrate stiffness and modulate behavior through the calpain-integrin-E-cadherin pathway. Beginning with the activation of calpain, a protease that modulates the cytoskeleton and E-cadherin, this pathway affects integrin B1, a receptor of extracellular matrix proteins. Piezo1 signaling ensures the proper localization to facilitate cell-matrix adhesion, cellular aggregation, and balance between proliferation with apoptosis. In endothelial cells, this homeostasis supports vascular development because integrins are crucial for angiogenesis.