Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in specific signaling in the thyroid gland. 3',5'-cyclic AMP + H2O = AMP + H(+) Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions. Inhibited by dipyridimole. Insensitive to selective PDE inhibitors including rolipram and milrinone as well as to the non-selective inhibitor, IBMX. Unaffected by cGMP. Purine metabolism; 3',5'-cyclic AMP degradation; AMP from 3',5'-cyclic AMP: step 1/1. Abundantly expressed in the thyroid. Also very weakly expressed in brain, spinal cord and placenta. In the thyroid isoform 1 predominates, and isoforms 2 and 6 are also highly expressed. In the placenta isoforms 1 and 2 are expressed equally. In the brain isoform 2 predominates. Composed of a C-terminal catalytic domain containing two putative divalent metal sites and an N-terminal regulatory domain. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. Major isoform. Belongs to the cyclic nucleotide phosphodiesterase family. PDE8 subfamily.