Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes (PubMed:15260978). May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents. 3',5'-cyclic AMP + H2O = AMP + H(+) Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions. Binds 2 divalent metal cations per subunit. Site 2 has a preference for magnesium and/or manganese ions. Inhibited by rolipram. Purine metabolism; 3',5'-cyclic AMP degradation; AMP from 3',5'-cyclic AMP: step 1/1. Interacts with DISC1. Additional isoforms seem to exist. Expressed in brain, heart, lung and skeletal muscle (PubMed:17519386). Expressed in white blood cells (PubMed:8392015). Brain-specific isoform. Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily. Extended N-terminus.