The stress response is one of the most fundamental biological phenomena of cells, and its disruption is a pathogenic factor in a wide variety of diseases, including cancer, neurodegenerative diseases, immune diseases, and metabolic diseases. This talk will focus mainly on our latest findings on cellular stress responses, especially osmotic responses.Cells are constantly exposed to stresses that force a change in volume due to the difference in osmotic pressure between the inside and outside of the cell (osmotic stress), and they maintain a constant cell volume by sensing and responding appropriately to osmotic pressure changes. Until now, most studies have been based on the idea that osmotic changes without physical substance are sensed via changes in the cell membrane in contact with the extracellular environment. Using the ASK3 protein as a research model, we have demonstrated that cells sense osmotic stress inside the cell, triggered by the physical phenomenon of liquid-liquid phase separation, using biochemical methods and computer simulations. I hope to introduce some aspects of stress signaling through this basic research on osmotic stress response.