Department of Molecular & Cellular Pathology, University of Dundee, Ninewells Hospital & Medical School, Dundee,Scotland, UK. p68 is a prototypic member of the ‘DEAD box’ family of RNA helicases and shows the characteristic RNA helicase activity associated with DEAD box proteins. It has been reported to be involved in both pre-mRNA and ribosomal RNA processing processes which are consistent with its acting as an RNA helicase. However recent data have indicated that p68 is also a potent transcriptional activator of Estrogen Receptor alpha (ER), a function that is independent of helicase activity. These findings suggest that p68 is a multifunctional protein, which plays a role in several cellular processes. The reports that p68 can co-activate ER function prompted us to examine its ability to co-activate other transcription factors. Accordingly we have shown that p68 can stimulate the activity of several other transcription factors in addition to ERincluding the tumour suppressor p53. In separate experiments we investigated whether p68 has an intrinsic ability to activate or repress transcription. In experiments involving co-transfection of cell lines with GAL4-p68 fusion expression plasmids, together with relevant reporter plasmids containing GAL4 DNA-binding elements, we showed that, in some contexts, p68 can also act as a transcriptional repressor and have mapped domains within p68 which are involved in transcriptional activation/repression. Our data highlight novel functions for the p68 RNA helicase, which are independent of helicase activity.