STUB1 and autosomal recessive cerebellar ataxia: Of the 13 exon mutations in CHIP found in ARCA patients, 9 affect either the charged linker region or the U-box domain (Figure 1a), which are domains required for CHIP function and/or dimerization.37,38 The identification of ataxia-associated mutations that abolish CHIP’s ubiquitination activity,9,18–21 in addition to recent reports of exome mutations in other proteins involved in ubiquitination in other ataxia-related conditions,39,40 support the distinct connection between neurological diseases and defects in the ubiquitin–proteasome system (UPS) (reviewed in references 41–44).