The Hedgehog (Hh) signaling pathway regulates body patterning and organ development during embryogenesis. In adults the Hh pathway is mainly quiescent, with the exception of roles in tissue maintenance and repair, and its inappropriate reactivation has been linked to several disparate human cancers. The Hh family of proteins in mammals comprises Shh (Sonic hedgehog), Ihh (Indian hedgehog) and Dhh (Desert hedgehog). Shh is the most widely expressed and the most actively investigated. When synthesized Shh gains entry to the secretory pathway and undergoes endoproteolysis to yield N-Shh (cholesterol-modified N-terminal fragment of Shh. N-Shh is subsequently palmitoylated at the N-terminal cysteine residue. Closely tied with the maturation and release of N-Shh are the actions of the protein Dispatched A. Once secreted, N-Shh exerts most, if not all, of its actions on target cells through Patched1 (Ptch1), a 12-pass TM (transmembrane) protein that, in the absence of N-Shh, represses the activity of a seven-pass TM protein, Smoothened (SMO). Binding of N-Shh to Ptch1 inhibits repression of SMO, leading to activation of some genes and de-repression of others through the effects of SMO on the Gli family of transcription factors. The SMO agonist purmorphamine (Axon 1690), for example, up-regulates gene expression of mediators of Hh pathway, SMO, PTCH1, GLI1, and GLI2. Signal initiation by N-Shh requires the formation of a ternary complex with Ptch1 and the protein BOC or CDO (both belonging to the Immunoglobulin superfamily of single-transmembrane proteins)