The article reviews the role of Piezo1, a mechanosensitive channel, in cell volume regulation. Piezo1 is a Ca²⁺-permeable channel that responds to mechanical stimuli such as membrane stretch and osmotic stress, leading to the influx of Ca²⁺ into the cell. This influx of Ca²⁺ is crucial for converting mechanical forces into cytosolic signals that control various cellular functions, including proliferation, apoptosis, and migration. The review highlights the importance of Piezo1 in erythrocyte volume regulation, where it helps in reducing cell volume to pass through narrow capillaries. In HEK293 cells, increased Piezo1 expression enhances regulatory volume decrease (RVD), the process of restoring cell volume after osmotic shock-induced swelling, through the modulation of volume-regulated anion channels (VRAC). In glioblastoma cells, Piezo1 controls RVD by modulating Ca²⁺-activated K⁺ channels (IK and BK). The review also discusses the physiopathological roles of Piezo1, including its involvement in erythrocyte dehydration, arterial smooth muscle rigidity, tumor malignancy, and cell migration and death. The authors conclude that Piezo1 plays a central role in regulating cell volume and that its activity is essential for maintaining cellular homeostasis.The article reviews the role of Piezo1, a mechanosensitive channel, in cell volume regulation. Piezo1 is a Ca²⁺-permeable channel that responds to mechanical stimuli such as membrane stretch and osmotic stress, leading to the influx of Ca²⁺ into the cell. This influx of Ca²⁺ is crucial for converting mechanical forces into cytosolic signals that control various cellular functions, including proliferation, apoptosis, and migration. The review highlights the importance of Piezo1 in erythrocyte volume regulation, where it helps in reducing cell volume to pass through narrow capillaries. In HEK293 cells, increased Piezo1 expression enhances regulatory volume decrease (RVD), the process of restoring cell volume after osmotic shock-induced swelling, through the modulation of volume-regulated anion channels (VRAC). In glioblastoma cells, Piezo1 controls RVD by modulating Ca²⁺-activated K⁺ channels (IK and BK). The review also discusses the physiopathological roles of Piezo1, including its involvement in erythrocyte dehydration, arterial smooth muscle rigidity, tumor malignancy, and cell migration and death. The authors conclude that Piezo1 plays a central role in regulating cell volume and that its activity is essential for maintaining cellular homeostasis.