Various striatal PDE isoforms are likely to be compartmentalized and differentially targeted to pre-, post-, and/or peri-synaptic sites (Xie et al., 2006; Nishi et al., 2008), which may explain why specific PDEs such as PDE10A are preferentially compromised in HD models (Hebb et al., 2004; Beaumont et al., 2016; Patel et al., 2018). The gene discussed is PDE10A; the disease is Huntington disease.