The fundamental importance of both cellular and systemic zinc homeostasis, achieved in part through the regulation of transmembrane zinc flux, is highlighted by the prevalence of human genes coding for zinc-containing proteins, which may comprise as many as 10% of all coding sequences. The multiple human transmembrane zinc transporters are classified as families SLC30 and SLC39. Members of the SLC39 family appear to be involved predominantly in cellular zinc efflux or intracellular sequestration in membrane-bound compartments, whereas transporters of the SLC39 familiar have, largely, a role in zinc transport in the opposite direction. Emerging evidence indicates that at least some zinc transporters can function bidirectionally (e.g. (Valentine et al., 2007). Regulation of epithelial zinc transport, consistent with systemic and/or cellular zinc homeostasis, is achieved, at least in part, though the regulated expression of zinc transporter genes, including at the level of transcription and through RNA stability. As an example, human intestinal zinc transporter expression was seen to be affected by daily oral zinc supplementation (Cragg et al., 2005), and numerous reports document changes in zinc transporter expression in response to changes in zinc availability in rodent and cell line models. Mechanisms of transcriptional regulation in response to zinc in mammalian cells, other than the well-characterised positive transcriptional response to zinc mediated by the transcription factor MTF1, are still to be uncovered. Transcriptional regulation of the SLC30A5 gene, which codes for the zinc transporter ZnT5, localised apically in the enterocyte, appears to provide a model system for the identification of a novel zinc-sensitive transcriptional regulatory pathway (Jackson et al., 2007); ongoing studies based on this response are aimed towards identification of a novel zinc-regulated transcription factor responsible for transcriptional repression at elevated zinc concentrations. Ageing may be associated with changes in epithelial zinc transport, including reduced dietary zinc absorption (Fairweather-Tait et al., 2007). We are currently investigating epigenetic processes as a possible mechanism through which ageing may result in reduced expression of intestinal zinc transporters and, thus, reduce dietary zinc absorption in older people. Abnormal expression of specific zinc transporters has been linked with cancer, including tumours of the breast and prostate (Hogstrand et al., 2009). The SLC30A5 gene is methylated in vivo and promoter methylation in vitro affects expression. In light of the well-established phenomenon that tumour tissue shows changes in DNA methylation compared with corresponding normal tissue, these observations suggest that zinc transporter gene methylation may be a factor in cancer development and/or progression.