Membraneless Organelles and Organ Fibrosis: New Perspectives and Therapeutic Opportunities

Organ fibrosis is a maladaptive repair outcome in which persistent injury drives extracellular matrix (ECM) accumulation, distortion of tissue architecture, and progressive loss of organ function. Although major fibrotic pathways are well established, it remains less clear how mechanical, inflammatory, oxidative, metabolic, and other stress signals are spatially organized and converted into persistent cell-state changes. Many biomolecular condensates, also known as membraneless organelles (MLOs), are organized through liquid–liquid phase separation (LLPS), which can alter signaling efficiency, transcriptional output, RNA handling, and stress responses. Increasing evidence links this mode of molecular organization to fibrosis-relevant pathways across the kidney, liver, cardiovascular system, and lung. In this review, we summarize current evidence for MLO-mediated regulation of organ fibrosis, discuss the potential to therapeutically modulate assembly, client recruitment, and material properties, and highlight key translational challenges, including in vivo causality, cell-type and disease-stage selectivity, delivery, and safety. Overall, MLOs provide a useful framework for understanding how fibrotic signals are organized and sustained, while also opening therapeutic opportunities beyond conventional single-node inhibition.