SLC26A4 encodes pendrin, a sodium-independent transporter mediating electroneutral exchange of chloride with bicarbonate, iodide, and formate in a 1:1 stoichiometric ratio 1234. Pendrin localizes to the apical plasma membrane of inner ear endolymphatic sac cells and is essential for normal endolymph reabsorption 5. SLC26A4 is the major genetic cause of hereditary hearing loss in Chinese populations, accounting for 87.59% of nonsyndromic enlarged vestibular aqueduct (EVA) cases and representing a critical gene alongside GJB2 for deafness pathogenesis 67. Mutations in SLC26A4 cause both Pendred syndrome (syndromic) and nonsyndromic autosomal recessive deafness with varying severity 89. Disease-associated variants typically impair pendrin function through multiple mechanisms: intracellular retention, reduced anion transport capability, or disrupted mRNA splicing 89. Recent studies identified exonic deletions and deep intronic variants expanding the mutational spectrum 10. Pendrin's plasma membrane abundance is regulated by interaction with clathrin-mediated endocytosis machinery via AP-2 mu2 subunit binding, providing insights into potential therapeutic intervention targets 5.