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ZIP14 is a metal transporter essential for the regulation of body manganese homeostasis. The physiological functions of ZIP14 have been uncovered mainly through two lines of in vivo studies that examined the phenotypes of ZIP14 loss, including studies of humans with ZIP14 mutations and animals with ZIP14 deficiency. This mini review aims at presenting an updated view of the important advances made towards understanding the genetic and pathological mechanisms of brain manganese overload caused by ZIP14 deficiency.