It has been known for several decades that protein aggregation is a hallmark of neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig's disease). It was assumed that these aggregations, which are closely associated with the lesions or plaques characteristic of these diseases, formed as a byproduct by the neurodegenerative disease process. This view of neurodegenerative diseases has changed dramatically over the last few years. It is now clear that protein aggregates are seen in the early stages of pathogenesis, suggesting that they are not the result of cellular damage. Furthermore, evidence that these insoluble complexes are cytotoxic and trigger apoptosis suggest that protein aggregation plays a seminal role in the etiology of neurodegenerative diseases.

New evidence extends these finding further by demonstrating that insoluble protein aggregates of non-disease related proteins are toxic to cells and that the ubiquitin, which is present in these protein aggregates, can trigger cell apoptosis. This new understanding of the seminal role that aggregates play in the etiology of neurodegenerative diseases has lead to a re-examination of the role of aggregation in other disease mechanisms. Recent evidence suggests that certain forms of liver disease, diabetes, systemic and localized amyloidosis are considered to involve protein misfolding and aggregation. With this increased understanding of the role of protein aggregation in the etiology of a variety of diseases, an understanding of the molecular mechanisms that underlay the process of protein aggregation is of increased importance.