Its role in the circulatory system extends beyond the heart, as Prdm16 loss in arterial endothelial cells (ECs) impairs arterial reperfusion of ischemic mouse limbs due to endothelial dysfunction, and <i>PRDM16</i> polymorphisms are associated with coronary artery disease.<h4>Methods</h4>Zebrafish were used to analyze vascular development, arteriovenous endothelial specification, and the emergence of arteriovenous malformations in the absence or presence of Prdm16 or Notch signaling. Here, PRDM16 is linked to coronary artery disorder.