PLN and heart disorder: 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.