THYROID peroxidase (TPO) is the primary enzyme involved in thyroid hormone synthesis, catalyzing iodide oxidation, iodination of tyrosine residues, and coupling of iodotyrosines to generate the iodothyronines T₃ and T₄ (1). It is a membrane-bound glycoprotein with a heme prosthetic group. In addition to the pivotal physiological role of TPO, there was strong immunological evidence, even before its molecular cloning, that this enzyme was the elusive “thyroid microsomal antigen” in autoimmune thyroid disease (discussed below).

The molecular cloning of the complementary DNA for a protein provides powerful new opportunities for studying protein structure and function at an unprecedented level of detail. In t h e past decade, three of the four major thyroid-specific proteins have been cloned, namely thyroglobulin (TG) (2–4), TPO (see below), and the TSH receptor (5–8). Molecular cloning of the thyroid iodide transporter may occur soon (9). As might be expected, these advances have been followed by an explosion of information regarding fundamental aspects of thyroid pathophysiological function. The goal of this review is to summarize and interpret new information on TPO that has accumulated since its molecular cloning.