Fig. 2. Protein condensation and protein homeostasis.

The protein homoeostasis system regulates the formation, clearance, composition, interactions, localisation and biophysical properties of protein condensates^146,147. Although the complete mapping of the protein homoeostasis system that controls protein condensates is still far from complete, several examples have already been identified. The formation and dissolution of the droplet state are regulated by post-translational modifications^23,24 and the availability of interaction partners²⁵. The re-localisation within a cell of solid-like condensates may revert them to the liquid-like state by making available suitable interaction partners^34,117. Molecular chaperones may interfere with misfolded protein intermediates and inhibit the formation of the amyloid state either from the native state through the deposition pathway or from the droplet state through the condensation pathway²⁷. Autophagy contributes to stress granule clearance²⁹, and the liquid-liquid phase separation of p62 with its ubiquitinated substrates may lead to autophagosome formation³⁰.