Phosphorylation of S/T-P motifs in proteins by proline-directed kinases(e.g. MAP kinases) is a major signalling mechanism. Some of the resulting phosphoproteins become substrates for the peptidyl-prolyl cis/trans isomerase Pin1; this provides a further level of regulation by inducing conformational changes that can have a profound effect on the activity, localization,phosphorylation status and stability of the protein. In a Commentary on p. 773, Kun Ping Lu and co-workers review work that indicates that Pin1 is a key regulator of cell proliferation. Depletion of Pin1 can cause mitotic arrest and apoptosis, and the enzyme has been shown to regulate synthesis of cyclin D1. Pin1 appears to target the transcription factor JUN and β-catenin, both of which activate the cyclin D1 promoter, and studies of Pin1-null mice have revealed that Pin1 directly stabilizes cyclin D protein. Furthermore, recent work shows that Pin1 also regulates the tumour suppressor p53 as part of the DNA damage response. Since Pin1 is expressed in several cancers, Lu and co-workers go on to discuss its potential as a target for anti-cancer therapy,suggesting that its high specificity makes it an attractive option.