DUOXA2 (dual oxidase maturation factor 2) is essential for thyroid hormone synthesis by enabling DUOX2 protein maturation and trafficking. DUOXA2 recruits DUOX2 from the endoplasmic reticulum to the apical plasma membrane 12, where the DUOX2-DUOXA2 complex catalyzes hydrogen peroxide (H2O2) production critical for thyroid peroxidase function 3. DUOXA2 mutations cause thyroid dyshormonogenesis, a major form of congenital hypothyroidism (CH) characterized by impaired thyroid hormone synthesis despite normal gland morphology 45. In Chinese populations, DUOXA2 variants occur in approximately 6.7% of CH patients and are particularly prevalent in thyroid dysgenesis cases (18.75%) 67. Mutations disrupting DUOXA2 function impair DUOX2 enzyme activity and H2O2 generation, leading to inherited CH typically following autosomal recessive inheritance 47. Clinically, DUOXA2-mutated patients tend to present milder disease with normal thyroid size compared to other genetic forms of CH 7. DUOXA2 gene screening enhances diagnostic accuracy when combined with screening of other dyshormonogenesis-related genes, supporting early intervention and personalized treatment planning in affected children 3.