LAUSR

The Hippo–YAP (Yes-associated protein) pathway is an evolutionarily and functionally conserved regulator of organ size and growth with crucial roles in cell proliferation, apoptosis, and differentiation. This pathway has great potential for therapeutic manipulation in different disease states and to promote organ regeneration. In this Review, we summarize findings from the past decade revealing the function and regulation of the Hippo–YAP pathway in cardiac development, growth, homeostasis, disease, and regeneration. In particular, we highlight the roles of the Hippo–YAP pathway in endogenous heart muscle renewal, including the pivotal role of the Hippo–YAP pathway in regulating cardiomyocyte proliferation and differentiation, stress response, and mechanical signalling. The human heart lacks the capacity to self-repair; therefore, the loss of cardiomyocytes after injury such as myocardial infarction can result in heart failure and death. Despite substantial advances in the treatment of heart failure, an enormous unmet clinical need exists for alternative treatment options. Targeting the Hippo–YAP pathway has tremendous potential for developing therapeutic strategies for cardiac repair and regeneration for currently intractable cardiovascular diseases such as heart failure. The lessons learned from cardiac repair and regeneration studies will also bring new insights into the regeneration of other tissues with limited regenerative capacity.This Review summarizes the current understanding on the roles of the Hippo–YAP pathway in cardiac development, growth, homeostasis, disease, and regeneration, with a particular focus on the roles of the Hippo–YAP pathway in endogenous cardiac muscle renewal, including the pivotal role of this pathway in regulating cardiomyocyte proliferation, differentiation, stress response, and mechanical signalling.Key pointsThe Hippo–YAP (Yes-associated protein) pathway is an evolutionarily conserved pathway that controls organ size.Hippo signalling restrains cardiomyocyte proliferation during development to control cardiac size.The Hippo–YAP pathway regulates the activity of growth pathways during prenatal and postnatal life and is important for cardiac homeostasis.Hippo signalling inhibits adult cardiac regeneration.The Hippo–YAP pathway regulates various events during cardiac regeneration, including cardiomyocyte proliferation and differentiation, injury resistance, stress response, and mechanical signals.Manipulating the Hippo–YAP pathway is a potential therapeutic tool for treating cardiac injury.