Taken together, the amplitude of SHH signaling is fine-tuned in part via the mechanism of p38α-mediated GLI1 phosphorylation on Ser937/Ser941 that substantially contribute to the incidence and severity of MBSHH and BCC, and intervention of this critical phosphorylation site of GLI1 may provide an additional approach for pharmacotherapy of these diseases. The gene discussed is SHH; the disease is skin basal cell carcinoma.