Importantly, it has always been assumed that mutant huntingtin is recognised as ‘foreign’ and consequently ubiquitinated and targeted for degradation by the ubiquitin-proteasome system pathway, because (1) a mutation in the gene coding for huntingtin causes HD, (2) mutant huntingtin is found in neuronal intranuclear inclusions, (3) neuronal nuclear inclusions are ubiquitinated, (4) the ubiquitin-proteasome pathway is responsible for recognising and disposing of abnormal proteins and (5) proteasome fragments are associated with NIIs. The gene discussed is HTT; the disease is Huntington disease.