GOF and LOF point mutations in the human TRPM4 gene have been linked to different forms of cardiac conduction defects, including progressive familial heart block type I,896,897 Brugada syndrome,898., 899., 900., 901. right-bundle branch block, atrioventricular block, and complete heart block.902., 903., 904. However, it remains puzzling why either reduced or increased TRPM4 activity leads to different forms of cardiac conduction defects. The gene discussed is TRPM4; the disease is third-degree atrioventricular block.