PDE4B is a member of the type IV, cyclic AMP (cAMP)-specific, cyclic nucleotide phosphodiesterase (PDE) family. Enzymes of the cAMP-dependent phosphodiesterase type 4 (PDE4) family are important in hydrolyzing cAMP produced by G-protein coupled receptor (GPCR) stimulated adenylyl cyclases. Four genes (PDE4A, B, C and D) make up the PDE4 family. cAMP-dependent phosphodiesterase type B (PDE4B) family consists of four known splice variants, PDE4B1, B2, B3 and a novel 66kD PDE4B4 protein. One or more subtype variants of PDE4B are ubiquitously present in all mammalian cells. In CNS, all four PDE4B subtype variants are expressed in varying ratios and their activity is regulated in tandem with GPCRs stimulation. Some PDE4B variants are also substrate for PKA-dependent phosphorylation. Peripheral tissues exhibit differential expression of PDE4B1, B2 and B4 variants; the PDE4B4 (66kD protein) is the major PDE4B variant expressed in lungs, testis and heart. In testis PDE4B enzymes are expressed in somatic cells (Sertoli and Leydig cells) while PDE4A is localized in germ cells.