Just as expected, the two ASOs targeting Rest E3 significantly induced ∆E3, reduced nuclear Rest and rescued neuronal gene expression in a cellular model of HD, while the ASOs‐induced transcriptional regulation was mimicked by siRNAs which considerably down‐regulate Rest mRNA expression, suggesting a causative link from ASOs‐induced ∆E3 to Rest activity. Here, REST is linked to Huntington disease.