The hedgehog signaling pathway is initiated by hedgehog (hh) ligand binding to the extracellular domain of patched receptor (ptc), leading to the derepression of smoothened (smo) activity. Activation of the atypical GPCR smo results in the accumulation of the transcriptional activator form of cubitus interruptus (ci) and the derepression/activation of hh target genes. In the absence of hh, smo is repressed by ptc and ci is processed to a truncated repressor form. (Adapted from FBrf0220683 and FBrf0231236).