Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 
(SCA3), may be the most common dominantly inherited ataxia in the world. Here I 
will review historical, clinical, neuropathological, genetic, and pathogenic 
features of MJD, and finish with a brief discussion of present, and possible 
future, treatment for this currently incurable disorder. Like many other 
dominantly inherited ataxias, MJD/SCA3 shows remarkable clinical heterogeneity, 
reflecting the underlying genetic defect: an unstable CAG trinucleotide repeat 
that varies in size among affected persons. This pathogenic repeat in MJD/SCA3 
encodes an expanded tract of the amino acid glutamine in the disease protein, 
which is known as ataxin-3. MJD/SCA3 is one of nine identified polyglutamine 
neurodegenerative diseases which share features of pathogenesis centered on 
protein misfolding and accumulation. The specific properties of MJD/SCA3 and its 
disease protein are discussed in light of what is known about the entire class 
of polyglutamine diseases.