Although some pharmacological tools demonstrated to increase pS13/pS16 HTT levels have shown benefit in animal and cellular models of HD, modifying different phenotypes including mutant HTT aggregation (Di Pardo et al, 2012; Alpaugh et al, 2017; Bowie et al, 2018), the lack of suitable direct genetic modulators of pS13/pS16 HTT levels have so far limited the capacity to determine if effects of phosphor-mimetic mutations are indeed a true phenocopy of increased phosphorylation. This evidence concerns the gene HTT and Huntington disease.