There are two routes of activation of the Gli transcription factor family: a) Hh ligand and Smo-dependent, which defines the classical canonical route in normal cells and ciliated tumours; and b) Smo-independent route via cross-talk with other signalling pathways, such as Transforming Growth Factor beta (TGFβ), MAPK and phosphoinositide 3-kinase (PI3K)/Akt signalling [59]. The gene discussed is GLI1; the disease is neoplasm.