Amongst Class F GPCRs, CG simulations of the hedgehog signal transducer Smoothened (SMO) predicted PI(4,5)P2 encounter complexes.158 This is intriguing as SMO signalling is intricately linked to primary cilia, a region which contains special zones of phosphoinositide enrichment.159 Joubert’s syndrome, a human ciliopathy characterized by impaired Hh signaling and human birth defects, can be caused from mutations in a 5-positon phosphatase (Inpp5e) which lead to alterations in the distribution of ciliary PI(4,5)P2. This evidence concerns the gene SMO and Joubert syndrome.