Abstract: Huntington’s disease (HD) is an inherited autosomal dominant neurodegenerative disorder characterized by the development of adult-onset motor dysfunction, psychiatric disturbances and intellectual decline. HD is associated with an expansion of CAG repeat sequence in the huntingtin gene (Htt). Exon 1 of Htt normally contains between 6 to 35 CAG repeats, whereas in patients affected with HD it contains more than 40 trinucleotides. The mutant Htt protein (mHtt) exhibits gain-of-toxic properties that cause neuronal dysfunction and death (Saudou and Humbert, 2016). Protein misfolding and aggregation is a common molecular feature of HD, suggesting that impairment in the buffer capacity of the proteostasis network contributes to the pathogenesis of the disease. Multiple studies in cell culture and animal models, in addition to the analysis of postmortem human tissue, have indicated that one of the main nodes of the proteostasis network affected in HD involves the function of the endoplasmic reticulum (Vidal et al., 2011). XBP1 is a master regulator of the unfolded protein response (UPR), the main adaptive pathway to cope with endoplasmic reticulum stress (Hetz et al., 2020). We previously reported that the genetic disruption of the transcription factor XBP1 delays disease progression and reduces protein aggregation in models of HD (Vidal et al., 2012), in addition to amyotrophic lateral sclerosis (ALS; Hetz et al., 2009), Parkinson´s disease (Valdes et al., 2014) and Alzheimer´s disease (Duran-Aniotz et al., 2017).