Piezo1 is a newly identified mechanosensitive channel involved in cell volume regulation. It is a Ca²⁺-permeable channel that responds to mechanical stimuli, including membrane stretch and osmotic stress, and is essential for converting mechanical forces into intracellular Ca²⁺ signals that regulate various cellular functions, such as migration and cell death. Piezo1 is expressed in multiple tissues and plays a crucial role in the regulation of cell volume, particularly in erythrocytes, where it helps reduce cell volume to pass through narrow capillaries. In HEK293 cells, increased Piezo1 expression enhances the regulatory volume decrease (RVD), a process by which cells restore their original volume after osmotic shock-induced swelling. Piezo1-mediated Ca²⁺ influx is used to modulate volume-regulated anion channels, which are essential for RVD. Recent studies have shown that Piezo1 also controls RVD in glioblastoma cells via the modulation of Ca²⁺-activated K⁺ channels. However, the mechanisms through which Piezo1 controls cell volume and maintains its homeostasis are still not fully understood. The present review aims to provide a broad overview of the literature discussing the recent advances on this topic. Piezo1 is a key player in cell volume regulation, and its activation is essential for various physiological processes, including cell migration, proliferation, and cell death. The role of Piezo1 in cell volume regulation is closely linked to the activation of Ca²⁺-activated K⁺ channels and the modulation of volume-regulated anion channels. The study highlights the importance of Piezo1 in maintaining cell volume homeostasis and its potential role in various diseases, including cancer and erythrocyte disorders. The findings suggest that Piezo1 is a critical component in the regulation of cell volume and that its activity is essential for various physiological processes. The review also discusses the molecular mechanisms underlying Piezo1's role in cell volume regulation and its potential therapeutic applications.Piezo1 is a newly identified mechanosensitive channel involved in cell volume regulation. It is a Ca²⁺-permeable channel that responds to mechanical stimuli, including membrane stretch and osmotic stress, and is essential for converting mechanical forces into intracellular Ca²⁺ signals that regulate various cellular functions, such as migration and cell death. Piezo1 is expressed in multiple tissues and plays a crucial role in the regulation of cell volume, particularly in erythrocytes, where it helps reduce cell volume to pass through narrow capillaries. In HEK293 cells, increased Piezo1 expression enhances the regulatory volume decrease (RVD), a process by which cells restore their original volume after osmotic shock-induced swelling. Piezo1-mediated Ca²⁺ influx is used to modulate volume-regulated anion channels, which are essential for RVD. Recent studies have shown that Piezo1 also controls RVD in glioblastoma cells via the modulation of Ca²⁺-activated K⁺ channels. However, the mechanisms through which Piezo1 controls cell volume and maintains its homeostasis are still not fully understood. The present review aims to provide a broad overview of the literature discussing the recent advances on this topic. Piezo1 is a key player in cell volume regulation, and its activation is essential for various physiological processes, including cell migration, proliferation, and cell death. The role of Piezo1 in cell volume regulation is closely linked to the activation of Ca²⁺-activated K⁺ channels and the modulation of volume-regulated anion channels. The study highlights the importance of Piezo1 in maintaining cell volume homeostasis and its potential role in various diseases, including cancer and erythrocyte disorders. The findings suggest that Piezo1 is a critical component in the regulation of cell volume and that its activity is essential for various physiological processes. The review also discusses the molecular mechanisms underlying Piezo1's role in cell volume regulation and its potential therapeutic applications.