 Pendrine is an anion exchanger protein found in the apical membrane of certain epithelial cells. It is responsible for regulating sodium and chloride levels in the body, and mutations in this gene can cause pendrid syndrome, a rare genetic disorder characterized by sensory neural hearing loss, hyperthyroidism, and low blood pressure. In this study, researchers determined the cryo-electron microscopy structures of mouse pendrine in both symmetric and asymmetric homodimers. They discovered that the asymmetric homodimer consists of one inward-facing protomer, and the other outward-facing protomer, representing simultaneous uptake and secretion of anions. This unique state of pendrine as an electroneutral exchanger provides insight into the properties of an anion exchange cleft and helps explain why certain disease-associated variants are important to understanding the Pendrine exchange mechanism. This article was authored by Chenying Liu, Xiong Zhong, Huihuan, and others.