In cancer, the mechanisms underlying the aberrant activation of canonical Hh are mainly due to the loss of PTCH-1 and -2 repressors, to the loss of GLI-inhibitory function of Suppressor of Fused homolog (SUFU), to activating mutation in SMO, or overexpression of pathway activators (SMO, GLI1, GLI2, Hh ligands) [24]. The gene discussed is GLI1; the disease is cancer.