The electrical rhythms underlying heart and brain function are sustained by proteins that form pores in cellular membranes that flux ions like calcium and sodium. These pores are anchored in place by a molecule called ankyrin-B (ANKB). We discovered a genetic change in the Gitxsan Nation of Norther BC that results in a version of ANKB (ANKB p.S646F) associated with heart defects at birth, arrhythmias, sudden death, seizures, and cerebral aneurysms. We showed that this version of the ANKB molecule is mishandled by immature heart cells; however, we do not fully understand how this ANKB version contributes to clinical manifestations. As a clinician-scientist and expert in microscopy-based measurement of cellular excitability, I am well-positioned to bridge this important knowledge gap. By imaging calcium and voltage changes in living cells, I will study the impact of partial loss of ANKB and expression of disease-associated ANKB p.S646F versions on heart and brain cell excitability. I will also compare heart cell excitability data with patient electrocardiograms to help understand the connections between fundamental laboratory and clinical observations.