Htt∗ has been shown to interfere with mitochondria, leading to reduction in mitochondrial trafficking (Orr et al., 2008), and reduced ATP content has been detected in synaptosomes fractions prepared from the brains of HD knock-in mice (Orr et al., 2008; Wang et al., 2008) These findings suggest that mitochondrial dysfunction may contribute to UPS impairment in HD by depleting critical ATP levels. Here, HTT is linked to Huntington disease.