Wolff-Parkinson-White (WPW) syndrome is the most common cause of ventricular pre-excitation, a condition where, due to defects in the conduction pathway, all or part of the ventricle is excited earlier than would normally be expected, often leading to ventricular fibrillation and sudden cardiac death. It was recently discovered that many of the underlying mutations responsible for the familial form of WPW syndrome are located in the gene encoding for the regulatory gamma(2)-subunit (PRKAG2) of the AMP-activated protein kinase. The cellular mechanisms for the observed arrhythmias are currently being studied and may involve glycogen storage with associated hypertrophy as well as alterations in the properties of cardiac ion channels such as voltage-gated sodium channel. It is the aim of this review to discuss our current knowledge of the cellular disturbances underlying the induction of arrhythmias in patients with PRKAG2 mutations.