IYD (iodotyrosine deiodinase) is a flavin-dependent enzyme that catalyzes the NADPH-dependent reductive dehalogenation of iodotyrosines, particularly monoiodotyrosine (MIT) and diiodotyrosine (DIT), during thyroid hormone biosynthesis 12. This enzyme facilitates iodide salvage by removing iodine from halogenated byproducts of thyroid hormone production, allowing the recovered iodide to re-enter hormone-producing pathways 3. IYD operates through a unique mechanism involving sequential one-electron transfer steps from reduced flavin to substrate, with a stabilized flavin semiquinone intermediate maintained by hydrogen bonding with a threonine residue 12. The enzyme shows broader substrate specificity, also catalyzing debromination and dechlorination of other halotyrosines 1. Mutations in IYD cause thyroid dyshormonogenesis 4, leading to congenital hypothyroidism through defective iodide recycling 34. However, population genetic studies indicate IYD mutations are relatively rare among congenital hypothyroidism cases, with carrier frequencies of approximately 0.08% in general populations 56. Recent research suggests IYD may have additional functions beyond thyroid metabolism, including potential roles in thermogenesis regulation 7.