Thyroid peroxidase (TPO) catalyzes the iodination of tyrosine (Tyr) residues of the thyroglobulin (TG) dimer, using iodide (I-) and hydrogen peroxide (H2O2) (Alexander, 1961; Nakamura et al., 1984; Taurog et al., 1996; Kessler et al., 2007). Cofactors of TPO are Ca2+ and Heme b (Baker et al., 2023). Eight Tyr residues on each TG monomer are monoiodinated, four of them will be iodine acceptors in the subsequent hormonogenic coupling reaction, and four are donors: Tyr-24, -108, -149, -243, -1310, -2540, -2573, and -2766 (Coscia et al., 2020). TPO can also form elemental iodine (I2) when no TG is immediately available (Lagorce et al., 1991).

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).