Because the Wnt signalling pathway plays crucial roles at several stages of epithelial and hair development (reviewed in12,13), we asked whether the pathogenic palmoplantar keratoderma effects of the PAWS1 mutations might be due to dysregulation of Wnt signalling or, alternatively, to other activities of the PAWS1 protein. The gene discussed is SACK1G; the disease is hereditary palmoplantar keratoderma.