The intra-cellular sites of toxic effects of proteins in polyQ disorders. PolyQ aggregates induce cytotoxic effects through a range of mechanisms. To form insoluble inclusions, compiling of polyQ-expanded protein provoke quality-control mechanisms including ubiquitin–proteasome system, chaperones and autophagy. By interacting with transcriptional factors, the toxic polyQ proteins could regulate transcriptional processes. Other cellular sites of toxic effects induced by polyQ mutant proteins include Ca2+ channel, mitochondria, and cytoskeleton with diverse abnormalities respectively.