Understanding liquid–liquid phase separation through TDP-43: fundamental principles, subcellular compartmentalisation, and role of solid inclusion formation
Abstract
Phase separation is an important process in biology associated with formation of membraneless organelles but possibly related to the emergence of solid inclusions. TDP-43 is a largely studied paradigmatic case, as it forms neuronal cytoplasmic inclusions in neurodegenerative diseases and is an essential component of many membraneless organelles. Here, we review the physicochemical fundamentals of liquid-liquid phase separation (LLPS) of TDP-43 and its fragments in vitro, showing that full-length TDP-43 requires RNA or chaperones to form stable liquid droplets. We describe TDP-43-containing membraneless organelles and the debate on whether these assemblies represent reservoirs for pathological solid inclusion formation.
Fields of Study & Subjects
RNA Research and Splicing
Amyotrophic Lateral Sclerosis Research
Neurogenesis and neuroplasticity mechanisms
Publication details
- Journal / source
- Genome biology
- Publisher
- Springer Science and Business Media LLC
- Volume
- 27
- Issue
- 1
- Publication date
- 29 January 2026
- Language
- EN