Schematic representation of VWF. VWF is synthesized as a pre-pro-VWF that comprises a 22-residue signal peptide, a 741-residue propeptide, and the 2050-residue mature subunit. After removal of the signal peptide (SP), pro-VWF subunits associate in the endoplasmic reticulum in “tail-to-tail” dimers by the formation of disulfide bonds between the cysteine-rich carboxyl-terminal CK domains, after which dimers further multimerize by forming “head-to-head” disulfide bonds between the amino-terminal cysteine-rich D3 domains in the Golgi. The propeptide and the mature subunit form pro-VWF (2791 residues) consisting of 4 types of repeated domains as indicated. Crystal structures for the A1⁶  and A3⁷  domains are depicted. The main binding sites that are important for the hemostatic function of VWF are indicated together with the ADAMTS13 cleavage site. Major regions in which mutations have been found that are associated with VWD types 1 and 2 are also shown.