Mechanosensitive calcium ion channels Piezo1: A therapeutic target in liver disease

The liver is vital in the metabolism of proteins, cholesterol, and carbohydrates, as well as energy production. Liver diseases often develop insidiously, making early diagnosis difficult, and rapid disease progression is directly associated with increased mortality risk. Ion channels, transmembrane proteins involved in various cellular functions, including development, migration, and programmed cell death, are associated with numerous diseases; however, the response of the liver to mechanical load and the underlying molecular mechanisms remain unclear. Piezo1, a mechanosensitive calcium ion (Ca²⁺ channel, is expressed in hepatic cholangiocytes, fibroblasts, stellate cells, Kupffer cells, and sinusoidal endothelial cells. Piezo1 has demonstrated potential relevance in liver pathophysiology; however, data on its therapeutic feasibility remain to be validated through systematic studies. This review aims to summarize Piezo1 expression and function; discuss its roles in fibrosis, hepatocellular carcinoma, iron metabolism disorders, and cholestasis; and distinguish established findings from hypotheses and highlight key gaps. Finally, considerations for the preclinical evaluation of Piezo1 modulators (e.g., in vitro assays, animal models, delivery, and safety) are outlined to guide translational research, rather than asserting definitive therapeutic efficacy at this stage.