Spinocerebellar ataxia 3 (SCA3), a neurodegenerative disease characterized mainly by progressive ataxia affecting balance, gait and speech, is caused by a mutation in the C-terminus polyglutamine (PolyQ) region of the ataxin-3 protein, an ubiquitously expressed deubiquitinating enzyme with important functions in the proteasomal protein degradation pathway and regulation of transcription. Here, ATXN3 is linked to Machado-Joseph disease.