Usually, wild-type ataxin-3 is a predominantly cytoplasmic protein; however, nuclear mislocalization and aggregation of mutant ataxin-3 in neuronal cells are crucial determinants of the disease protein toxicity and the molecular pathogenesis in MJD (Paulson et al., 1997; Schmidt et al., 1998). The gene discussed is ATXN3; the disease is Machado-Joseph disease.