Von Willebrand disease (VWD) is the most common inherited bleeding disorder and results from quantitative or qualitative defects in von Willebrand factor (VWF) protein, which is a key protein for platelet adhesion and stabilizing factor VIII. This presentation will go over the history, clinical presentation, and discuss MADD variants and other factors affecting the level of protein. We will discuss how MADD variants can disrupt normal signaling and alter vesicular trafficking pathways in this emerging intersection of molecular signaling and disease.