(A) Disp-mediated Shh extraction and handover to Scube2. (B) Lipidated Hh/Shh relay from the plasma membrane to soluble lipoprotein acceptors. (C) Disp-mediated cholesterol export to lipoprotein acceptors (left) depletes the plasma membrane of free cholesterol and is strongly associated with Scube2-assisted proteolytic Shh release, possibly by depleting lipid rafts of cholesterol and in turn allowing sheddase access to the substrate (right). This model integrates the established roles of Disp, Scube2, and lipoproteins in regulated Shh release and signaling.