Fig. 4: Proposed model for the role of sortilin in TG trafficking.

a Both TG and sortilin exist in monomeric and dimeric forms. The SorTG complex is established primarily between the monomeric forms of both proteins. Acidic pH conditions promote sortilin dimerisation and ligand release. b Secreted dimeric TG (dTG) can exist in both iodinated and uniodinated forms. Extracellular degradation of both forms is likely generating either a relaxed or a monomeric TG state (mTG). In these species the exposed TG C-terminal peptide (orange) is recognised by sortilin. Hence, sortilin-mediated TG trafficking to the lysosome leads to the release of thyroid hormones (TH) from iodinated TG.