Missense variants in SHP2 result in aberrant regulation of the RAS/MAPK signaling pathway, leading to profound effects associated with several human diseases, including developmental disorders such as LEOPARD syndrome (LS) and Noonan syndrome (NS), as well as cancers such as juvenile myelomonocytic leukemia (JMML). The gene discussed is PTPN11; the disease is Noonan syndrome with multiple lentigines.