Thyroid peroxidase (TPO) is the key enzyme involved in thyroid hormone synthesis. Autoantibodies to TPO (TPOAbs) are a hallmark of autoimmune thyroid disease (AITD). Here, we highlight recent progress over several years in understanding TPO biochemistry and function in various pathologies. TPO undergoes complex post-translational modifications as a dimer in endoplasmic reticulum during secretory pathway to apical membrane of thyrocytes. In silico modelling of TPO dimer has provided new information into the two enzyme active site regions and autoantigenic determinants. TPO and hydrogen peroxide generating DUOX and caveolin-1 form a complex known as thyroxisome to bring together in close proximity the components of hormone synthesis in apical membrane. Autoimmunity to TPO is characterised by autoantibodies and T cell reactivity in Hashimoto's disease and Graves' disease. TPOAbs are directed predominantly to two immunodominant determinants (IDR) termed IDR-A and IDR-B regions, with the latter antibodies more predominant in autoimmune disease. Strong genetic risk has been shown to be associated with TPOAbs for AITD development. A different antibody with unusual features of bispecificity for both TPO and thyroglobulin may play protective role in Hashimoto's disease. In the context of TPO biology in human cancer, thyroid tumor tissue and breast cancer differ in TPO expression and isoform composition. In thyroid cancer, TPO expression is decreased partly by the BRAF(V600E) mutation, with direct impact on significant hormone production. TPOAbs may play a protective role in breast cancer development. An understanding of TPO and its unique two enzymatic active sites and autoantigenic determinants continues to add new knowledge on the biochemistry and immunology of this enzyme.

甲状腺过氧化物酶（TPO）是参与甲状腺激素合成的关键酶。TPO自身抗体（TPOAbs）是自身免疫性甲状腺疾病（AITD）的标志。在这里，我们重点介绍了近年来在了解TPO生物化学和各种病理学功能方面的最新进展。TPO经历复杂的翻译后修饰，成为内质网的二聚体，并分泌到甲状腺细胞的顶膜。在计算机上TPO二聚体的建模为两个酶活性位点区域和自身抗原决定簇提供了新信息。TPO和产生过氧化氢的DUOX和Caveolin-1形成一种复合物，称为甲状腺溶酶体，可将顶端膜中激素合成的各个组分紧密结合在一起。对TPO的自身免疫的特征在于桥本病和Graves病中的自身抗体和T细胞反应性。TPOAb主要针对两个称为IDR-A和IDR-B区域的免疫决定簇（IDR），后一种抗体在自身免疫性疾病中更为主要。业已证明，强烈的遗传风险与AITD发育的TPOAb相关。具有不同的TPO和甲状腺球蛋白双特异性特征的不同抗体可能在桥本氏病中起保护作用。在人类癌症中的TPO生物学方面，甲状腺肿瘤组织和乳腺癌在TPO表达和同工型组成方面有所不同。在甲状腺癌中，BRAF（V600E）突变会部分降低TPO的表达，直接影响大量激素的产生。TPOAb可能在乳腺癌的发展中起保护作用。对TPO及其独特的两个酶活性位点和自身抗原决定簇的了解继续为该酶的生物化学和免疫学增加了新的知识。