The last ten years have witnessed major advances in our understanding of zi
nc transporters and their regulation in eukaryotic organisms. Two families
of transporters, the ZIP (Zrt-, Irt-like Protein) and CDF (Cation Diffusion
Facilitator) families, have been found to play a number of important roles
in zinc transport. These are ancient gene families that span all phylogene
tic levels. The characterized members of each group have been implicated in
the transport of metal ions, frequently zinc, across lipid bilayer membran
es. This remarkable conservation of function suggests that other, as yet un
characterized members of the family, will also be involved in metal ion tra
nsport. Many of the ZIP family transporters are involved in cellular zinc u
ptake and at least one member, the Zrt3 transporter of S. cerevisiae, trans
ports stored zinc out of an intracellular compartment during adaptation to
zinc deficiency. In contrast, CDF family members mediate zinc efflux out of
cells or facilitate zinc transport into intracellular compartments for det
oxification and/or storage. The activity of many of these transporters is r
egulated in response to zinc through transcriptional and post-transcription
al mechanisms to maintain zinc homeostasis at both the cellular and organis
mal levels.