“…Aberrant regulation of SHP2 activity is closely implicated in RAS-MAPK pathway-associated genetic and developmental diseases, called RASopathies. They include various cancers such as neuroblastoma, lung cancer, colon cancer, juvenile myelomonocytic leukemia, and acute myelogenous leukemia (Huang et al, 2014;Zhang et al, 2015;Asmamaw et al, 2022) and developmental disorders such as Noonan syndrome and LEOPARD syndrome 1 (Tartaglia et al, 2001;Siegfried et al, 2017). Critically, a number of shp2 genetic mutations have been reported in RASopathy patients, most of which interfere with the inhibitory recognition of the phosphatase domain by N-SH2, leading to uncontrolled upregulation of its activity (Siegfried et al, 2017;Dong et al, 2021).…”