By activating the cGMP-dependent protein kinase (PKG), phosphodiesterase 5 (PDE5) inhibition by sildenafil slows down cardiac disease progression in a mouse model of CryABR120G-based cardiac proteinopathy (Ranek et al., 2013); and inhibition of PDE1 induces cAMP-dependent protein kinase (PKA) and PKG-mediated promotion of proteasomal degradation of misfolded proteins and thereby effectively treats diastolic malfunction and delays premature death in CryABR120G-based cardiac proteinopathy mice (Zhang et al., 2019). Here, PRKG1 is linked to heart disorder.