Cellular zinc (Zn 2+) homeostasis is essential to human health and is under tight regulations. Human zinc trans-porter 1 (hZnT1) is a plasma membrane–localized Zn 2+ exporter belonging to the ZnT family, and its functionalaberration is associated with multiple diseases. Here, we show that hZnT1 works as a Zn2+/Ca2+ exchanger. Wedetermine the structure of hZnT1 using cryo–electron microscopy (cryo-EM) single particle analysis. hZnT1 adoptsa homodimeric structure, and each subunit contains a transmembrane domain consisting of six transmembranesegments, a cytosolic domain, and an extracellular domain. The transmembrane region displays an outward-facing conformation. On the basis of structural and functional analysis, we propose a model for the hZnT1-mediated Zn2+/Ca2+ exchange. Together, these results facilitate our understanding of the biological functions ofhZnT1 and provide a basis for further investigations of the ZnT family transporters.