The mechanism/s by which mutated huntingtin impairs Nrf2 signalling are unclear, but may involve the tumor suppressor protein homologous to the E6-AP carboxyl terminus domain and ankyrin repeat containing E3 ubiquitin-protein ligase 1 (HACE1), which has been found to facilitate Nrf2 signalling, and is decreased in the striatum of Huntington’s disease post-mortem brain and cultured mouse striatal cells expressing mutated huntingtin [194]. The gene discussed is NFE2L2; the disease is juvenile Huntington disease.