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Lysosomes are emerging as important players in cellular zinc ion (Zn 2+ ) homeostasis. The series of work on Zn2+ accumulation in the neuronal lysosomes and the mounting evidence on the role of lysosomal Zn 2+ in cell death during mammary gland involution set a biological precedent for the central role of the lysosomes in cellular Zn 2+ handling. Such a role appears to involve cytoprotection on the one hand, and cell death on the other. The recent series of work began to identify the molecular determinants of the lysosomal Zn 2+ handling. In addition to zinc transporters (ZnT) of the solute-carrier family type 30A (SLC30A), the lysosomal ion channel TRPML1 and the poorly understood novel transporter TMEM163 have been shown to play a role in the Zn 2+ uptake by the lysosomes. In this review, we summarize the current knowledge on molecular determinants of the lysosomal Zn 2+ handling, uptake, and release pathways, as well as discuss their possible roles in health and disease.

The mucolipin-1 TRPML1 ion channel transmembrane-163 TMEM163 protein and lysosomal zinc handling