Polyglutamine (polyQ) diseases are a kind of neurodegenerative disorders caused by unstable repeat expansion of CAG trinucleotide in the specific gene sequences. Nine types of polyQ diseases have been discovered, and most of the pathogenic proteins play an important role in transcriptional regulation in disease pathology. The abnormal repeat expansion of glutamine in polyQ protein will cause protein misfolding and thereby form aggregates accumulated in cells. The protein aggregates can sequester transcription factors, ubiquitin (Ub) adapters or receptors, molecular chaperones and other cellular factors into aggregates or inclusions through specific interactions mediated by their own domains, RNAs or Ub conjugates. Decrease of the soluble fractions and available amounts of these essential factors will impair the cellular function of transcriptional regulation and cause pathogenic transcriptional disorders. Therefore, studying polyQ-expanded protein aggregation that may sequester cellular transcription factors and other components will be beneficial to elucidating the pathogenesis of polyQ diseases at the molecular level, and provide potential therapeutic strategy for clinical application.