For over 100 years after the first description of the disorder, the molecular 
pathology underlying the deafness and thyroid pathology in Pendred syndrome (PS) 
remained unknown. In 1997, early progress towards understanding the molecular 
basis of the disorder was made when we identified the PS gene and found it to 
belong to the SLC26 family of anion transporters. The realization that an anion 
transporter was responsible for these clinical features soon highlighted a 
potential role for pendrin in thyroid hormone biosynthesis. The role of pendrin 
in deafness, however, remained unclear. Our determination of its expression 
pattern in the inner ear along with the development of a mouse with a targeted 
disruption of the Slc26a4 gene has revealed that Slc26a4 is expressed in areas 
of the endolymphatic compartment known to play a role in endolymph reabsorption 
and that absence of this protein leads to a profound prenatal endolymphatic 
hydrops and destruction of many of the epithelial cells surrounding the scala 
media. The precise mechanisms underlying endolymph reabsorption in the inner ear 
are not yet known; these studies, however, provide some of the groundwork for 
allowing the future delineation of these processes.