The Hedgehog (Hh) signal transduction pathway plays a key role in both mammalian and insect development. In addition, when the pathway is inappropriately activated by mutation, it contributes to the development of a common form of human skin cancer. Chamoun et al. show that the secreted Hh protein in the fruit fly Drosophila is palmitoylated at its amino terminus and that this modification is essential for the activity of Hh in embryonic and larval patterning. Genetic experiments indicate that the acyltransferase that catalyzes this modification is encoded by the Skinny hedgehog (ski) gene. The ski gene is related in sequence to a gene required for the Wingless signaling pathway, and its function raises the possibility that acylation of secreted proteins may play a widespread role in development (see the Perspective by Van den Heuvel).Z. Chamoun, R. K. Mann, D. Nellen, D. P. von Kessler, M. Bellotto, P. A. Beachy, K. Basler, Skinny Hedgehog, an acyltransferase required for palmitoylation and activity of the Hedgehog signal. Science 293, 2080-2084 (2001). [Abstract] [Full Text]M. van den Heuvel, Fat hedgehogs, slower or richer? Science's STKE (2001), http://www.stke.org/cgi/content/full/OC_sigtrans;2001/100/pe31. [Abstract] [Full Text]