Hypoplastic left heart syndrome (HLHS) is a complex congenital heart disease characterized by abnormal development of the left ventricle, mitral valve, aortic valve, and ascending aorta proximal to the entrance of the ductus arteriosus. Abnormal circulation leads to the patent foramen ovale and ductus arteriosus, and enlarged right atrium, right ventricle, and pulmonary artery (Fig. 1). Based on the status of aortic and mitral valves, two types are established: aortic and mitral atresia, and aortic and mitral stenosis. In the most severe cases with both aortic and mitral atresia, the left ventricle is absent or slit-like and the aortic arch is shrunken, whereas in the other less severe cases, the ventricular hypoplasia is variable (Brekke 1953). In recent decades, numerous genetic variants and molecular pathways associated with the etiology of HLHS have been identified. Nevertheless, a comprehensive understanding of the intricate cellular and molecular interactions that lead to the observed anomalies in patients with HLHS remains elusive.