Thyroglobulin (Tg) is a glycoprotein with a predominant form as a 600 kDa homodimer. Tg, the precursor of the thyroid hormones, is synthesized by the thyrocytes and transported to the apical surface where it is secreted into the lumen of thyroid follicles and stored as the major component of colloid (>95%). A minor proportion of Tg is found as 330 kDa monomers or as tetramers. Reduction or degradation of 660 kDa or 330 kDa Tg molecules can lead to the formation of smaller polypeptides, some of which are present in trace amounts in the colloid. At the cell-colloid interface, post-transitional modifications of Tg occur, which are characterized by coupling of tyrosyl residues with iodide, leading to the formation of thyroid hormone residues within Tg molecule. Hormone release generally requires uptake of Tg from the colloid by thyrocytes and proteolytic cleavage along the lysosomal pathway.