Hirschsprung disease is an inherited or sporadic condition in humans, and is associated with mutations in genes encoding two pairs of extracellular ligand/receptor signaling molecules: the endothelin ligand EDN3 and its G-protein-coupled receptor (GPCR) EDNRB, and the receptor tyrosine kinase RET and its ligand GDNF (Parisi and Kapur, 2000). The gene discussed is EDNRB; the disease is Hirschsprung disease.