Abstract: The present invention relates to a heretofore uncharacterized family of cyclic nucleotide phosphodiesterases (CN PCD8) and provides specific polynucleotide and amino acid sequences which encode and identify CN PDE8 family members designated herein as CN PDE8A and CN PDE8B. The present invention also relates to the use of proteins, peptides and organic molecules capable of modulating CN PDE8 activity to inhibit or enhance phosphodiesterase activity associated with disease. The present invention further relates to the use of CN PDE8 and genetically engineered host cells that express CN PDE8 to evaluate and screen for substances and compounds that modulate cyclic nucleotide phosphodiesterase activity. The present invention also provides for cn pde8 antisense molecules. The invention provides genetically engineered expression vectors and host cells for the production of purified CN PDE8 polypeptide.