However, it is highly likely that ATX3 deficiency exert its pathogenic effect independent of its deubiquitination function, since Machado-Joseph disease is a triplet (CAG encoding glutamine, Q) repeat expansion disorder whereby ATXN3 mutant proteins accumulate as toxic insoluble protein aggregates (Chai et al., 1999). This evidence concerns the gene ATXN3 and Machado-Joseph disease.