Polyglutamine (polyQ)-expanded proteins form cytoplasmic aggregates that interfere with cellular protein quality control systems. Park et al. studied how polyQ proteins disrupt the clearance of misfolded proteins by the ubiquitin–proteasome system. They found that the degradation of a misfolded mutant version of cytosolic carboxypeptidase fused to GFP (CG*), which is normally degraded in the nucleus, was inhibited by co-expression of polyQ proteins, and that CG* accumulated in the cytoplasm. A quantitative interactome analysis revealed that polyQ aggregates sequester the yeast Hsp40 chaperone Sis1p (and one of its mammalian homologues, DNAJB1), and that this causes impaired CG* degradation. Importantly, the authors show that the function of Sis1p is to transport CG* from the cytoplasm to the nucleus for degradation.