Fig. 1.

Timeline of key milestones in the study of biomolecular phase separation. The concept of biomolecular phase separation has developed through nearly two centuries of scientific observation, originating with the identification of the nucleolus as the first recognized membraneless subcellular structure in 1835. In 2009, P granules were shown to exhibit spontaneous condensation and dissolution behaviors. Subsequent studies in 2011 confirmed that the nucleolus also displays LLPS-like properties. In 2012, in vitro reconstitution of LLPS highlighted the critical role of multivalency and IDRs in condensate formation. The pathological relevance of biomolecular phase separation emerged in 2015 with the identification of aberrant condensates in neurons, implicating dysregulated biomolecular phase separation in neurodegenerative disease. Mechanistic insights into LLPS-mediated malignant transformation were provided in 2021, linking condensate dynamics to cancer progression. Most recently, in 2023, studies have demonstrated that pharmacologically targeting oncogenic condensates can disrupt biomolecular phase separation and may offer therapeutic potential in cancer treatment