Hippo Signaling: Advances in Potential Therapeutic Targets for Sinoatrial Node Disorders

The cardiac conduction system (CCS) propagates electrical impulses, generates cardiac contractions, and ultimately ensures regular heartbeats. Disruptions within the CCS lead to cardiac arrhythmias, which are known to be the leading cause of cardiac-related mortalities in humans. The sinoatrial node (SAN) is a key component of the CCS and functions as the natural cardiac pacemaker to initiate normal cardiac impulse and conduction. The SAN is characterized by significant heterogeneity and contains various cell types, including pacemaker cells that spontaneously generate action potentials to maintain a constant beating rhythm. The fundamental Hippo signaling pathway plays a key role in heart development and regeneration. Recently, the Hippo signaling pathway is indicated as a critical pathway for maintaining SAN homeostasis, suggesting therapeutic targets for SAN disorders. This mini-review focuses on the recent molecular and mechanistic findings of Hippo's involvement in regulating SAN homeostasis and discusses potential new therapeutic targets for SAN pathologies.