Given the primary role of PDEs in the metabolism of cAMP and cGMP, isoform selective PDE inhibitors have been advanced as therapeutic agents for slowing disease progression in preclinical models of HD (Giampa et al., 2009a, b, 2010) and alleviating motor and cognitive symptoms in HD (Beaumont et al., 2016). The gene discussed is ALDH7A1; the disease is Huntington disease.