Hedgehog signaling uses lipid metabolism to tune smoothened activation.

In this issue of Developmental Cell, Yavari et al. reveal that membrane phosphatidylinositol-4 phosphate (PI4P) controls the activation of Hh signal transduction. Their data suggest that Ptc functions directly or indirectly to suppress accumulation of PI4P. Binding of Hh to Ptc derepresses PI4P levels, which in turn promotes Smo activation. (c) 2010 Elsevier Inc. All rights reserved.