For example, SUMOylation reduces polyQ toxicity in HD, SCA1, and SCA7 (Steffan et al., 2004; Janer et al., 2010; Guo et al., 2014; Wan et al., 2018; Marinello et al., 2019); however, SUMOylation of ataxin-3 increases its affinity to VCP, a protein that enhances ataxin-3 aggregation and exacerbates toxicity (Wang et al., 2006; Zhong and Pittman, 2006; Zhou et al., 2013; Almeida et al., 2015; Ristic et al., 2018; Johnson et al., 2021). Here, ATXN3 is linked to Huntington disease.