Kramer and colleagues go further in this paper by identifying a potential therapeutic avenue based on reducing the expression of C9orf72. Work in Huntington’s disease (HD) and on C9orf72 suggests two major mechanisms by which such expansions can cause disease: RNA toxicity by aggregation of RNA transcribed from the repeats into intracellular foci that disrupt cellular machinery, and protein toxicity by aberrant translation of the repeat mRNA into toxic dipeptide repeat proteins (DPRs). The gene discussed is C9orf72; the disease is juvenile Huntington disease.