Molecular genetic analyses have elucidated a class of inherited neurodegenerative disorders caused by expanded CAG repeats encoding polyglutamines (e.g. Huntington disease and Machado-Joseph disease). Proteins containing expanded polyglutamine repeats appear to precipitate by self-aggregation and, as a result, produce a core disease-related phenotype: neuronal cell death or degeneration. In other neurodegenerative disorders, such as Alzheimer disease, prion disease, Parkinson disease and amyotrophic lateral sclerosis, precipitation of abnormal proteins is also now considered to play a key role. These observations might lead to the elucidation of universal mechanisms for neurodegeneration and to effective treatments for many neurodegenerative disorders.