Adult-specific Tbx5 loss-of-function mice have spontaneous AF mediated through a Tbx5/Pitx2 gene regulatory network involving membrane effector genes, such as sodium voltage-gated channel alpha subunit 5 (Scn5a, which encodes the main voltage-gated sodium channel in the heart, Nav1.5), gap junction protein alpha (which encodes connexin 43), and calcium handling genes (28). The gene discussed is TBX5; the disease is atrial fibrillation.