PDEs are ubiquitously present in different tissues and cells. Their function is to hydrolyze cAMP and cGMP and to maintain their homeostasis for normal physiological processes. There are 11 different members of the mammalian class PDE superfamily (PDE1 through PDE11) with multiple genes and splicing variants. Given their varying roles, there are at least a 100 different PDE proteins characterized in eukaryotes. They are localized in different cellular compartments to regulate the duration and amplitude of cyclic nucleotide signaling within subcellular domains such as the cytosol and plasma membrane. 
Notably, although PDEs of the same family show divergence in their amino acid sequences, they are functionally related and can share similar substrates. Furthermore, PDEs can be either cAMP-specific or cGMP-specific, or they can hydrolyze both cyclic nucleotides; for example, PDE2 allows for cross-regulation of the cAMP and cGMP pathways. PDEs are thought to be excellent targets for manipulating levels of cyclic nucleotides because they are essentially viewed as end-stage regulators of signal transduction mediated by these important second messenger molecules. Due to their unique tissue distribution, structural properties, and functional properties, these enzymes have been hypothesized to be as potential targets for pharmacological inhibition.


1.Wahlang B,et al. Cell Signal. 2018;49:105–115.