In addition to the well-known molecules, new members have been discovered, such as Ellis-van Creveld Syndrome (EVC) and Ellis-van Creveld Syndrome 2(EVC2), which interact with SMO and control HH signaling activity by regulating SuFu/GLI3 dissociation and GLI3 trafficking in primary cilia of chondrocytes and osteoblasts (Caparrós-Martín et al., 2013; Palencia-Campos et al., 2017). This evidence concerns the gene GLI3 and Down syndrome.