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A protein’s function depends on a precise quaternary structure. However, when that structure is disrupted through misfolding, not only does the protein lose its function, but it runs the risk of aggregating. Protein aggregation cascades are integral in the pathophysiology of proteinopathies such as prion disease and Alzheimer's disease, where they ultimately lead to atrophy and death. This Collection invites submissions which advance our understanding of the mechanisms of protein misfolding and clearance, and interventions directed at reducing protein aggregates.