Metastable biological matter in liquid phase separation

Abstract Membraneless organelles (MLOs) are likely assembled via liquid–liquid phase separation (LLPS). The liquid‐like MLOs afford multifold peculiarities including high dynamics, reversibility and responsiveness. It is common to see fast, drastic, and reversible formation and dissolution events of MLOs, as well as transition into more stable glassy or gel‐like states, which suggests a metastable assembly state. Moreover, the alteration of metastability of LLPS is linked with cellular pathology. Here, we review the “metastability” related to MLOs driven by liquid phase separation, from multifaceted regards including energy state, molecular interactions, molecular structure, phase transition, as well as the associations with diseases. This review can help to advance the insight into properties and pathogenesis associated with LLPS of biological matter.