SMAD4 and hereditary hemorrhagic telangiectasia: SMAD4 regulation of CK2 has clinical relevance as patients with hereditary hemorrhagic telangiectasia (HHT) suffer from arteriovenous malformations, which have been linked to decreased SMAD4 as this causes unregulated CK2 phosphorylation of PTEN, which is then unable to repress phosphoinositide 3-kinase (PI3K)/AKT signaling [80].