Weighing in on molecular anchors: the role of ankyrin polypeptides in human arrhythmia

Loss-of-function gene variants which affect the biophysical properties of ion channel proteins have long been associated with the destabilization of cardiac electrical activity, leading to human arrhythmia and sudden cardiac death. However, recent studies have also demonstrated the importance of ion channel/transporter-anchoring molecules for normal cardiac function. Ankyrins are a family of membrane adaptor proteins whose role in metazoan physiology has been elucidated over the last quarter of a century, but with great strides taken in the last half decade with regard to cardiac cell physiology. The association of dysfunction in ankyrin-based cellular pathways with abnormal human cardiac function represents a surprising turn in the genetics of arrhythmias and sudden cardiac death, demonstrating an exciting new player in the field of ‘channelopathies’.