Stress granules (SG) are membrane-less compartments involved in regulating mRNAs 
during stress. Aberrant forms of SGs have been implicated in age-related 
diseases, such as amyotrophic lateral sclerosis (ALS), but the molecular events 
triggering their formation are still unknown. Here, we find that misfolded 
proteins, such as ALS-linked variants of SOD1, specifically accumulate and 
aggregate within SGs in human cells. This decreases the dynamics of SGs, changes 
SG composition, and triggers an aberrant liquid-to-solid transition of in vitro 
reconstituted compartments. We show that chaperone recruitment prevents the 
formation of aberrant SGs and promotes SG disassembly when the stress subsides. 
Moreover, we identify a backup system for SG clearance, which involves transport 
of aberrant SGs to the aggresome and their degradation by autophagy. Thus, cells 
employ a system of SG quality control to prevent accumulation of misfolded 
proteins and maintain the dynamic state of SGs, which may have relevance for ALS 
and related diseases.