About 30% of human medulloblastomas exhibit constitutive Shh pathway activation [44], resulting from either inactivating mutations in the negative regulators Patched1 (Ptch1) or Suppressor of Fused (Sufu), or from activating mutations in the signal transducing receptor Smoothened (Smo) or amplification of the Gli2 transcription factor [42, 45-47]. The gene discussed is GLI2; the disease is medulloblastoma.