In the absence of SHH ligand, the 12-transmembrane protein, PTCH1 inhibits the 7-transmembrane GPCR, namely smoothened (SMO), by preventing SMO from translocating into the primary cilia, and thereby blocks GLI transcription factors from moving to the nucleus, where GLI transactivates SHH target genes to promote cancer cell growth and metastasis [30,31]. The gene discussed is GLI1; the disease is cancer.