Abstract
Liquid-liquid phase separation (LLPS), the unmixing of inhomogeneous fluids into two or more phases, is emerging as a paradigm for the formation of a myriad of membraneless compartments inside cells (1, 2). This type of spatial organization, in contrast to membrane-bound compartmentalization, has long lacked unifying principles. However, the physiological relevance of compartmentalization through LLPS inside cells is still poorly understood and often speculative. Additionally, regulatory mechanisms through which cells control and exploit LLPS are still emerging. On page 1210 of this issue, Garcia Quiroz et al. (3) show that keratohyalin granules (KGs) that are formed during epidermal differentiation in the skin are pH-sensitive liquid-like protein condensates. Formation of KGs may be physiologically important because mutations that cause defects in this process are associated with the common skin barrier defect ichthyosis vulgaris.