Our studies in genetic mouse models with either cardiomyocyte- (13) or fibroblast-restricted deletion of GC-B reveal that endogenous local CNP, elevating intracellular cGMP levels in cardiomyocytes and especially in fibroblasts, targets both components of diastolic stiffness; it enhances the phosphorylation of titin and thereby titin-based cardiomyocyte distensibility (13) and it counteracts pathological profibrotic and prohypertrophic CF activation (present study). The gene discussed is TTN; the disease is cystic fibrosis.