Huntington’s disease (HD) is a progressive neurodegenerative condition caused by the abnormal expansion of a polyglutamine tract in the N-terminus of the huntingtin protein. Over the last 20 years, HD pathogenesis has been explained by the generation of N-terminal fragments containing the polyglutamine stretch. A new study from Frederic Saudou’s group now investigates the function of the C-terminal fragments generated upon cleavage and shows that these products may also contribute to cellular toxicity in HD (El-Daher et al, 2015).