Previous studies show that the β1-adrenoceptor-induced cellular signalling is highly regulated by the receptor-associated PDE4D isoforms (De Arcangelis et al., 2009; Fu, Kim, et al., 2014; Richter et al., 2008), raising the possibility that PDE4D isoforms may be directly involved in regulating PKA phosphorylation of PLB at the SERCA2a complex in cardiac diseases. This evidence concerns the gene PDE4D and heart disorder.