The p21‐activated kinase 1 (Pak1) signalling pathway in cardiac disease: from mechanistic study to therapeutic exploration

p21‐activated kinase 1 (Pak1) is a member of the highly conserved family of serine/threonine protein kinases regulated by Ras‐related small G‐proteins, Cdc42/Rac1. It has been previously demonstrated to be involved in cardiac protection. Based on recent studies, this review provides an overview of the role of Pak1 in cardiac diseases including disrupted Ca2+ homoeostasis‐related cardiac arrhythmias, adrenergic stress‐ and pressure overload‐induced hypertrophy, and ischaemia/reperfusion injury. These findings demonstrate the important role of Pak1 mediated through the phosphorylation and transcriptional modification of hypertrophy and/or arrhythmia‐related genes. This review also discusses the anti‐arrhythmic and anti‐hypertrophic, protective function of Pak1 and the beneficial effects of fingolimod (an FDA‐approved sphingolipid drug), a Pak1 activator, and its ability to prevent arrhythmias and cardiac hypertrophy. These findings also highlight the therapeutic potential of Pak1 signalling in the treatment and prevention of cardiac diseases.