Multiple mechanisms of neuronal injury involve toxic RNA gain-of-functions, haploinsufficiency as well as protein gain-of-functions via canonical translation of proteins with extended polyQ domains and/or RAN translation of toxic repeat polypeptides which have been characterised in vitro in 13 reporter repeat expansion cell models and in patient bio-samples from seven diseases, including SCA8, DM1 [45,106], C9ORF72-ALS [49–51,120] and HD [52]. The gene discussed is RAN; the disease is Huntington disease.