DIO1 encodes iodothyronine deiodinase 1, a selenoprotein critical for thyroid hormone metabolism 1. DIO1 catalyzes multiple deiodination reactions essential for thyroid hormone activation and inactivation: it converts L-thyroxine (T4) to the active hormone 3,5,3'-triiodothyronine (T3) via outer-ring deiodination, and produces reverse T3 (rT3) via inner-ring deiodination 2. As a selenoprotein, DIO1 requires selenium for enzymatic function 1. DIO1 expression is transcriptionally regulated by T3 itself and influenced by genetic polymorphisms; the SNP rs2235544 in DIO1 associates with levothyroxine dose requirements in hypothyroid patients, enabling personalized dosing strategies 3. DIO1 deficiency manifests clinically as abnormal thyroid hormone metabolism, characterized by elevated reverse T3 levels and impaired T3 production 2. Recently, inherited human DIO1 mutations have been identified, causing reduced enzyme velocity and substrate affinity, representing the first documented cases of congenital D1 deficiency in humans 2. Additionally, DIO1 is underexpressed in thyroid carcinomas, particularly papillary thyroid cancers, suggesting potential roles in thyroid tumor pathogenesis 4.