Inappropriate Hh signaling has been ascribed to either ligand-dependent, i.e. autocrine and/or paracrine signaling, or ligand independent tumor cell intrinsic pathway activation due to loss-of-function mutations in PTCH or SUFU and gain-of-function mutations in SHH, SMO or GLI1/2 [5, 15]. The gene discussed is GLI1; the disease is neoplasm.