cAMP-hydrolyzing cyclic nucleotide phosphodiesterase (PDE) catalyzes hydrolysis of the cyclic nucleotides cAMP and cGMP to the corresponding nucleoside 5-prime-monophosphates. PDEs are key enzymes in signaling pathways that influence smooth muscle tone regulation. The PDE1 family are calmodulin-dependent (CaM-PDEs) that undergo stimulation through a calcium-calmodulin complex. Human PDE1B (PDE1B1) protein is present in neuronal cells of the cerebellum, hippocampus, and caudate, and lymphoblastoid lines, such as RPMI-8392 cells. PDE1B may participate in learning, memory, and regulation of phosphorylation of DARPP-32 in dopaminergic neurons. A splice variant known as PDE1B2 encodes a 516-amino acid protein and diverges from PDE1B1 by the replacement of the first 38 residues with an alternative 18 residues. The human PDE1B gene maps to chromosome 12q13, contains 13 exons, and encodes a 536 amino acid protein.