Lack of one or both lipid modifications results in diminished signalling activity of the protein.11 As a result, many mutations of Shh found in genetic diseases, such as holoprosencephaly, are associated with defects in catalysis of processing,12,13 suggesting that cholesterol processing of the Shh precursor is essential for the activation of appropriate Shh signalling pathways. The gene discussed is SHH; the disease is holoprosencephaly.