Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (PubMed:32025030, PubMed:17532758). The synthesis of T3 and T4 involves iodination of selected tyrosine residues of TG/thyroglobulin followed by their oxidative coupling in the thyroid follicle lumen (PubMed:32025030). Following TG re-internalization and lysosomal-mediated proteolysis, T3 and T4 are released from the polypeptide backbone leading to their secretion into the bloodstream (PubMed:32025030). One dimer produces 7 thyroid hormone molecules (PubMed:32025030). Monomer (PubMed:32025030). Homodimer (via ChEL region); occurs in the endoplasmic reticulum and is required for export to the Golgi apparatus (PubMed:32025030). Homooligomer; disulfide-linked; stored in this form in the thyroid follicle lumen (PubMed:8626858). Secreted into the thyroid follicle lumen (PubMed:19509106). Localizes to colloid globules, a structure formed in the thyroid follicle lumen consisting of cross-linked TG arranged in concentric layers (PubMed:8626858, PubMed:11082042). Specifically expressed in the thyroid gland. The cholinesterase-like (ChEL) region is required for dimerization and export from the endoplasmic reticulum. Iodinated on tyrosine residues by TPO (PubMed:2760035, PubMed:32025030). There are 4 pairs of iodinated tyrosines used for coupling: acceptor Tyr-24 is coupled to donor Tyr-149 or Tyr-234, acceptor Tyr-2573 is coupled to donor Tyr-2540, acceptor Tyr-2766 in monomer 1 is coupled to donor Tyr-2766 in monomer 2 and acceptor Tyr-1310 in monomer 1 is coupled to donor Tyr-108 in monomer 2 (PubMed:32025030). Sulfated tyrosines are desulfated during iodination. Undergoes sequential proteolysis by cathepsins to release thyroxine (T4) and triiodothyronine (T3) hormones. In the thyroid follicle lumen, cross-linked TG (storage form) is solubilized by limited proteolysis mediated by cathepsins CTSB and/or CTSL. Partially cleaved TG is further processed by CTSK/cathepsin K and/or CTSL resulting in the release of T4. Following endocytosis, further processing occurs leading to the release of T3 and more T4 hormones. The disease is caused by variants affecting the gene represented in this entry. Disease susceptibility is associated with variants affecting the gene represented in this entry. Belongs to the type-B carboxylesterase/lipase family. The cholinesterase-like (ChEL) region lacks the Ser residue of the catalytic triad suggesting that it has no esterase activity. Thyroglobulin entry