The nonselective HDAC inhibitor suberoylanilide hydroxamic acid was shown to ameliorate the motor phenotype in R6/2 mice.55 Although compounds targeting HDAC1 and HDAC3 have been shown to ameliorate disease phenotypes in fly and cellular models,56 systematic work has shown HDAC4 to be the sole HDAC among 11 whose genetic knockdown ameliorates the HD phenotype in mouse models.57–60 HDAC4 inhibition has therefore been a focus for therapeutic development in HD, and potent, selective small-molecule inhibitors of its enzymatic function have been developed.61 This evidence concerns the gene HDAC9 and Huntington disease.