Liquid–liquid phase separation (LLPS) of biomolecules drives the formation of cellular compartments, which determines cell plasticity and fate decision. Emerging evidence indicates that a large number of membraneless organelles (MLOs), including nucleoli, Cajal bodies, P-bodies, and stress granules, exist as liquid droplets within the cell and orchestrate the cell plasticity control in response to the dynamics of extracellular cues. The MLOs provide not only organizers for signaling cascade but also nano-reactors for signaling catalysis (Liu et al., 2020). However, the molecular mechanisms underlying MLO dynamics and its relation to the cell plasticity control have remained elusive (Alberti and Hyman, 2021). MLO assembly is tightly regulated in the intracellular environment, and failure to control its dynamic properties often leads to protein misfolding and aggregation, which perturbs cell plasticity and elicits pathogenic reaction. In this special issue, we describe the mechanisms and regulation of condensate assembly and dissolution, highlight recent advances in understanding the role of biomolecular condensates in aging and disease, and discuss how cellular stress, aging-related loss of homeostasis, and a decline in protein quality control may contribute to the formation of aberrant, disease-causing condensates.