A small fraction of TG tyrosines are incompletely iodinated, depending on iodide availability. TPO catalyzes the transfer of a 4-hydroxy-3,5-diiodophenyl moiety from a donor diiodotyrosine (DIT) residue to an acceptor monoiodotyrosine (MIT) residue, consuming H2O2 and forming T3 on the acceptor and dehydroalanine on the donor residue (Taurog et al., 1996). In this example reaction a total of seven T3 molecules are synthesized per TG dimer: each dimer has two of the Tyr-24, Tyr-1310, and Tyr-2573 acceptor residues (one per monomer) and a single Tyr-2766 acceptor at the dimer interface (Coscia et al., 2020). This is also called the thyroid hormonogenic coupling reaction.

TPO is part of the thyroxisome, a complex consisting of at least Dual oxidase (DUOX1/2) (Fortunato et al., 2010), Dual oxidase maturation factor 1/2 (DUOXA1/2) (Grasberger & Refetoff, 2006) and Thioredoxin domain-containing protein 11 (TXNDC11, EFP1) (Wang et al., 2005), which is bound to Caveolin-1 (CAV1) (Senou et al., 2009) structures on the extracellular side of the apical plasma membrane of thyroid cells (reviewed in Godlevska & Banga, 2019; Jing & Zhang, 2022).

Mutations in the TPO gene can cause Thyroid dyshormonogenesis 2A (TDH2A; MIM:274500; see, e.g. Calaciura et al., 2002; Wu et al., 2002).