Phase separation as a physical organizing principle for membrane traffic

Vesicle trafficking is a core process for cellular material exchange and signal transduction, and its precise execution depends critically on the spatiotemporal coordination of regulatory molecules. In recent years, liquid–liquid phase separation (LLPS) and the resulting biomolecular condensates have been proposed as a mesoscale organizing principle within cells. This Review systematically surveys the emerging roles of LLPS in vesicle trafficking, proceeding from the physicochemical properties of molecular condensates. We focus on three major aspects: how membrane-associated phase separation lowers the energetic barriers to membrane bending and fusion through wetting, interfacial tension, and mesoscale assembly; how condensates act as molecular dispatchers to mediate short-distance vesicle transport, stress-induced flux regulation, and membrane identity switching; and how aberrant condensate behavior represents a shared mechanism in neurodegenerative diseases, viral infections, and cancer, with targeting condensate material states offering a new class of therapeutic strategies.