Since ATXN3 and the E3 ligase CHIP are both activated by mono-ubiquitination (Todi et al., 2009; Scaglione et al., 2011) preventing their deubiquitination may preserve their activity in HD, which might be especially interesting for CHIP as it can facilitate mHTT degradation via the proteasome (Figure 2). This evidence concerns the gene ATXN3 and Huntington disease.