In various types of cancer, including ovarian (5), lung (6,7), breast (8), prostate (9), endometrial (10), skin (11) and gastrointestinal (12–14), aberrant activation of Smo genes and loss of function mutations in the ptch gene relieve the suppression of the Smo protein and trigger full-length Gli1 translocation into the nucleus, prompting excessive activation of downstream genes, including c-myc and vascular endothelial growth factor (VEGF). The gene discussed is SMO; the disease is cancer.