Summary: Phosphodiesterases (PDEs) play an important role in dynamic regulation of cAMP and cGMP signaling. PDE10A is a dual substrate PDE highly expressed in striatal medium spiny neurons. PDE10A inhibitors can improve the cognitive symptoms of schizophrenia, and exhibit potential therapeutic value for Huntington"s disease. PDE10A1 is located in cytosol, whereas PDE10A2 is a membrane-associated protein. The assay is based on the generation of FAM-labeled nucleotide monophosphates by the phosphodiesterase. These phosphate groups bind to terbium-labeled nanoparticles, resulting in energy transfer from the terbium to the FAM, which emits a fluorescent signal at 520 nm. The change in fluorescent intensity can be easily measured using a fluorescence plate reader.