Since phosphodiesterase 10A (PDE10A) was first cloned and characterized in 1999 [1], significant investigation into the biological relevance of the protein and identification of enzyme inhibitors has been conducted. Understanding of the enzyme localization has led to the pursuit of PDE10 inhibitors as a potential target for treating central nervous system (CNS) disorders [2]. PDE10A is primarily expressed in the medium spiny neurons of the striatum, leading to significant investigation as to whether PDE10A has a potential role in treating movement disorders. PDE10A affects the same pool of cyclic adenosine monophosphate (cAMP) that dopamine (D2) neurons modulate, and thus schizophrenia research has been at the forefront [3]. Numerous reports have highlighted that PDE10A inhibitors are active in preclinical models where the marketed antipsychotics show efficacy. These include reductions in locomotor activity and conditioned avoidance responding. More recently, research has also disclosed that PDE10A inhibitors may have therapeutic potential in the treatment of Huntington's disease with activity in transgenic mouse models [4].Aside from the heavily studied CNS function of PDE10A, there are a few new reports of PDE10A localization and function outside the basal ganglia. One report finds the PDE10A protein expression in rat retina to be equivalent to the amount of expression of PDE10A in the striatum [5]. PDE10A protein expression is also abundant in photoreceptors and neurons in the inner nuclear layer of the retina. Evidence for the role of PDE10A in managing daily circadian rhythms is supported by the change in mRNA and protein levels in response to changes in the light cycle. Another report finds that PDE10A is a critical regulator of cAMP and cAMP response element-binding protein (CREB) in pulmonary arterial smooth muscle cells [6]. Rats with monocrotaline-induced pulmonary hypertension were dosed for 35 days with papaverine, and this resulted in 40-50% reduction in the hemodynamic effects of pulmonary hypertension and pulmonary vascular remodeling.