The vascular smooth muscle cell is an example of a cell that retains its capability to switch phenotype through adult life – from a contractile cell to a non-contractile, proliferating and migratory cell. This capability is important in physiology but also contributes substantially to vascular diseases including neointimal hyperplasia. An emerging feature of the phenotypic switch is that it is accompanied by change in the selection of ion channels made by the cell. Some of the change is known to be functionally important because blocking key ion channels suppresses proliferation, migration and neointimal hyperplasia (Kumar et al. 2006; Xu et al. 2006). Other cell types undergo similar changes and so there may be common underlying mechanisms. Regulatory networks at the transcriptional level are clearly implicated and emerging features will be reviewed. The lecture will focus on REST (repressor element-1 transcription factor), recently shown to be a repressor of the KCNN4 gene, which encodes a critical potassium channel (KCa3.1) in cell proliferation (Cheong et al. 2005). REST is down-regulated in cell proliferation and regulates expression of other relevant ion channels. We are working on the hypothesis that REST has a role in orchestrating changes in ion transport associated with cell phenotype switching.