DUOXA2 is a maturation factor essential for proper thyroid function. It facilitates the transport of the DUOX2 protein from the endoplasmic reticulum to the apical plasma membrane, enabling formation of a functional complex that generates hydrogen peroxide for thyroid hormone synthesis. Biallelic DUOXA2 mutations cause autosomal recessive congenital hypothyroidism (CH) through impaired maturation and cellular localization of DUOX2 1. In Chinese populations, DUOXA2 variants account for approximately 6.7% of CH cases and rank prominently among dyshormonogenesis genes, with the p.Y246X variant being a common hotspot 2. Patients with DUOXA2 mutations typically present with milder phenotypes and normal thyroid size compared to other genetic forms of CH 1. Although DUOX2 mutations are substantially more frequent than DUOXA2 mutations in CH cohorts, oligogenic inheritance patterns involving multiple DUOX system genes are prevalent, complicating genotype-phenotype correlations 31. Early DUOXA2 genetic screening combined with screening of other CH-related genes improves diagnostic accuracy and enables timely intervention with levothyroxine replacement to prevent neurodevelopmental impairment in affected infants 4.