JMML is an aggressive pediatric myeloid neoplasm with a dysregulated RAS/MAPK signaling pathway due to, most frequently, either heterozygous somatic gain-of-function mutations in KRAS, NRAS, or PTPN1 or germline RASopathy mutations in NF1 or CBL tumor suppressors with subsequent biallelic inactivation in hematopoietic cells, resulting in JMML [37]. The gene discussed is PTPN1; the disease is RASopathy.