Iodination and coupling of the hormonogenic tyrosines in thyroglobulin to yield the thyroid hormones T(3) and T(4). 2 H(+) + H2O2 + 2 iodide = diiodine + 2 H2O [thyroglobulin]-L-tyrosine + H(+) + H2O2 + iodide = [thyroglobulin]-3-iodo-L-tyrosine + 2 H2O [thyroglobulin]-3-iodo-L-tyrosine + H(+) + H2O2 + iodide = [thyroglobulin]-3,5-diiodo-L-tyrosine + 2 H2O 2 [thyroglobulin]-3,5-diiodo-L-tyrosine + H2O2 = [thyroglobulin]-dehydroalanine + [thyroglobulin]-L-thyroxine + 2 H2O [thyroglobulin]-3,5-diiodo-L-tyrosine + [thyroglobulin]-3-iodo-L-tyrosine + H2O2 = [thyroglobulin]-3,3',5-triiodo-L-thyronine + [thyroglobulin]-dehydroalanine + 2 H2O Binds 1 Ca(2+) ion per heterodimer. Binds 1 heme b (iron(II)-protoporphyrin IX) group covalently per heterodimer. Hormone biosynthesis; thyroid hormone biosynthesis. Interacts with DUOX1, DUOX2 and CYBA. Heme is covalently bound through a H(2)O(2)-dependent autocatalytic process. Heme insertion is important for the delivery of protein at the cell surface (By similarity). Cleaved in its N-terminal part. Defects in TPO are the cause of congenital hypothyroidism with goiter, a simple autosomal recessive trait observed in Toy Fox Terriers (TFTs). Neonatal affected pups exhibited inactivity, abnormal hair coat, stenotic ear canals, and delayed eye opening. Palpable ventrolateral cervical swellings were evident by 1 week of age. Serum thyroid hormone and thyroid-stimulating hormone concentrations were low and high, respectively. Histologic examination of the cervical masses disclosed cuboidal to columnar follicular epithelial cell hyperplasia with widely varying follicular size, shape, and amount of colloid. Oral thyroid hormone replacement therapy restored near-normal growth and development. At 8 weeks of age, radioiodine uptake and perchlorate discharge testing indicated an iodine organification defect. Biochemical analysis of thyroid tissue from affected dogs demonstrated enzymatic iodine oxidation deficiency and lack of sodium dodecyl sulfate-resistant thyroglobulin dimers, suggesting thyroid peroxidase deficiency. Belongs to the peroxidase family. XPO subfamily.