Dentatorubral-pallidoluysian atrophy (DRPLA) is a lethal neurodegenerative disorder caused by pathogenic expansion of CAG repeats within the atrophin-1 (ATN1) gene. As DRPLA belongs to the broader class of repeat expansion disorders (RED) that are driven by toxic gain-of-function effects, reduction or elimination of ATN1 expression is predicted to provide therapeutic benefit.