In the Ihh pathway, because PTHrP is a target gene of Ihh signaling, disruption of PTHrP or its receptor PTH/PTHrP-R results in skeletal dysplasia, premature maturation of chondrocytes, and excessive bone formation, and causes a lethal phenotype (Karaplis et al., 1994; Lanske et al., 1996). The gene discussed is PTHLH; the disease is skeletal dysplasia.