Metal transporter ZIP13 at the crossroads of intracellular zinc and iron homeostasis

Zinc and iron are essential trace elements indispensable for life in all organisms. However, even when these metals are sufficiently supplied to cells, the disruption of their proper distribution among intracellular organelles can lead to various diseases. ZIP13, a member of the Zrt-, Irt-like protein (ZIP) transporters that is localized to the endoplasmic reticulum (ER) and Golgi apparatus, was originally identified as an intracellular zinc transporter, but was recently shown to also transport iron ions. The dysfunction of ZIP13 disrupts metal distribution in the ER and Golgi apparatus, thereby impairing the homeostasis and function of various tissues. In this review, we summarize current understanding of ZIP13 biology, highlight its dual roles in zinc and iron transport, and discuss future perspectives on how ZIP13 research may provide new insights into the mechanisms underlying diseases associated with dysregulated intracellular metal homeostasis.