Since TPO plays a cardinal role in regulating many cellular processes of thyroid hormone biosynthesis in thyrocytes, it is important to present a summary of the impact that TPO research on the basis of molecular structure has had on our understanding of thyroid diseases. This review has therefore been written to highlight the biochemical, molecular biological, immunological and clinical aspects of TPO in thyroid follicular cells. As for hormonogenesis, further details of the properties of the superoxide generating system remain unknown, but based on decisive evidence showing what active iodinating species are at initial and principal stages, a novel concept of the mechanism of two electron oxidation has been put forth. Recent progress in studies of analyses of TPO gene structure has also provided stimuli for renewed investigation into a much wider field of thyroidology, including thyroiditogenesis.