Primary cilia are known to be key sites of Hedgehog (Hh) signal transduction in vertebrate cells, but the underlying molecular mechanisms are poorly understood. Rajat Rohatgi and colleagues now identify a new ciliary subdomain called the EvC zone that has an important role in transducing Hh signals (Dev. Cell 23, 823–835, 2012). The authors show that the products of the EVC and EVC2 genes, which are disrupted in the human ciliopathies Ellis-van Creveld syndrome and Weyers acrofacial dysostosis, colocalize at a region of the ciliary membrane immediately adjacent to the transition zone. They further show that disease-causing mutations that result in Evc2 mislocalization throughout the entire ciliary membrane disrupt Hh signaling downstream of Smoothened (Smo). At the biochemical level, they observe that Smo forms a complex with Evc and Evc2 in response to Hh pathway stimulation. On the basis of their findings, the authors propose that interactions between Smo and the Evc-Evc2 complex at the EvC zone facilitate the critical signaling events leading to the cilia-dependent activation of Gli transcription factors in response to Hh signal.