These results are in line with previous studies showing that Htt inclusions formed in HD patients or several cellular and in vivo models sequester several key components of the UPS system, including 26S proteasomes64 (ADRM165), deubiquitinases66 (e.g., NEDD4 and USP5), and E3 ubiquitin ligases (e.g., ITCH, TRAF6, UBE3A, UHRF2, and Parkin) and induce impairment of the UPS67–69. Here, HTT is linked to Huntington disease.