The idea that water-mediated protein interactions are important for PS was first put forward by Zaslavsky et al., who proposed that the alteration of the water structure due to the presence of the macromolecules contributes to PS . In a recent all-atom MD study of homotypic condensates formed by the LCD of FUS, Mukherjee and Schäfer investigated the interplay between protein-and solvation-related contributions to the formation of biomolecular condensates. The thermodynamic driving forces for LLPS were studied by decomposing the total free-energy change upon condensate formation (∆G) into the enthalpy (∆H) and entropy (-T ∆S) contributions, which were again further broken down into protein-protein, protein-water, and water-water contributions. The "thermodynamics bookkeeping" approach revealed that the -T ∆S contribution associated with the release of restricted water molecules from the dense protein droplet into the surrounding dilute phase upon condensate formation outweighs the penalty paid by the confined water molecules that are retained inside the dense phase. In effect, the solvation-related thermodynamic driving forces are favorable for PS -surprisingly, this contribution is even as large as that of the preferential protein-protein interactions in the dense phase. Qualitatively similar results were also found in a combined allatom MD/THz spectroscopy study of the human eye lens protein γD-crystallin, a phase-separating globular protein . Taken together, these findings may provide the molecular-level explanations for a more recent suggestion that condensates enable biological cells to elicit a fast response to perturbations by buffering the intracellular water potential .