Research progress on the regulatory role and mechanisms of the Hippo signaling pathway in the pathogenesis of congenital heart disease

Congenital heart disease (CHD) is the most common birth defect, with a complex pathogenesis involving genetic, environmental, and signaling pathway abnormalities. The Hippo signaling pathway is an evolutionarily conserved key regulator of organ size and tissue homeostasis. Its core components mammalian sterile 20-like kinase 1/2 and large tumor suppressor kinase 1/2 phosphorylate the downstream effectors YAP/TAZ, regulating cell proliferation, differentiation, and apoptosis. Dysfunction of the Hippo pathway is closely related to the occurrence and development of multiple CHD types. This review summarizes the core components and regulatory mechanisms of the Hippo pathway, describes its role in cardiac development, and elucidates the molecular mechanisms by which it contributes to ventricular septal defect, tetralogy of Fallot, and left ventricular noncompaction cardiomyopathy, aiming to provide a new theoretical basis for the early diagnosis and treatment of CHD.