Abstract

Von Willebrand Factor (VWF) is a large, multimeric glycoprotein essential for primary hemostasis, bridging the gap between vascular injury and platelet plug formation. This review explores the molecular and cellular biology of VWF, focusing on its complex life cycle within endothelial cells and megakaryocytes. VWF is synthesized as a precursor, pro-VWF, which undergoes dimerization and multimerization within the endoplasmic reticulum and Golgi apparatus. A critical step involves its packaging into specialized storage organelles, the Weibel-Palade bodies (WPBs) in endothelial cells, where it is stored in a highly condensed, helical tubular form. The process of regulated secretion from WPBs, which involves membrane fusion and exocytosis, is central to its function, allowing for the rapid release of ultra-large VWF multimers upon cellular activation. The manuscript details the structural specializations of VWF that enable its dual function: mediating platelet adhesion to the subendothelium under high shear stress and acting as a carrier protein for coagulation Factor VIII. Furthermore, it examines the pathological implications of VWF dysregulation, including Von Willebrand Disease (VWD), a common inherited bleeding disorder, and its role in thrombotic microangiopathies. By integrating insights into VWF biosynthesis, secretion, and clearance, this work highlights the factor's critical role at the interface of cell biology and vascular medicine, providing a comprehensive framework for understanding its involvement in both health and disease states.