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Membrane cholesterol impinges on signal transduction in several ways, which is highlighted in particular by the Hedgehog signaling pathway. In Hedgehog signaling, cholesterol is important for ligand biogenesis, as well as for signal transduction in receiving cells. Hedgehog ligands are post-translationally modified by cholesterol, and the Hedgehog receptor, Patched, is structurally similar to the Niemann–Pick C1 protein, which functions in intracellular lipid transport. Although the exact role of cholesterol in Hedgehog signal transduction remains elusive and is probably multifaceted, studies over the past year have implicated raft membrane subdomains, cholesterol transport and a link between protein and lipid trafficking in endocytic compartments.