The invention relates to phosphodiesterase PDE2A isoforms, as well as nucleic acids encoding such polypeptides. The invention further relates to methods for utilizing such polypeptides in diagnostic assays and in methods of screenin potential modulators, especially inhibitors, of the novel PDE2A disclosed herein. The polypeptides of the invention are involved in many physiological processes including, e.g. the formation of memory, cognitive function, and other disease and conditions which involve or are mediated by PDE2A and its signaling pathways.