See related article, pages 703–711 Since the first electron-microscopic description of the intercalated disc over half a century ago, it has become increasingly clear that this apparently simple boundary between individual cardiomyocytes exhibits a highly complex structural and molecular makeup which conveys a number of different key functions. Adherens junctions and desmosomes (“adhesion junctions”) within the intercalated disc are tied up by linker proteins to cytoskeletal proteins of neighboring cardiomyocytes, thus resulting in a network of proteins which is strong enough to absorb mechanical forces exerted during contraction. Secondly, gap junctions consisting of tightly packed connexins permit intercellular exchange of small molecules and excitatory current flow between neighboring cells, the latter being a prerequisite for the safe and rapid propagation of electrical activation along the network of cardiomyocytes. Thirdly, there exists evidence that a number of ion channels like sodium channels and potassium channels are targeted to the intercalated disc with as yet not fully defined functional consequences for the excitation process of cardiac tissue.1 Whereas all of these components of the intercalated disc are topologically segregated and serve distinct functions, recent studies of gene mutations which afflict structural proteins of the intercalated disc suggest that there exists extensive crosstalk between both mechanical and electrical junctions at the molecular level which ultimately can predispose the heart to arrhythmias. Whereas the topological segregation of adhesion junctions and gap junctions might be interpreted as a sign of structural independence between these 2 major components of the intercalated disc, a number of observations in fact suggests that the presence of stable mechanical contacts based on adhesion junctions is of paramount importance for both the formation and stabilization of functional …