Our findings that pathological activation of MAPK causes lymphangiectasia dovetail with recent studies identifying Noonan’s syndrome patients with chylothorax, lymphedema, and pleural effusion and gain-of-function mutations in components of the MAPK signaling pathway, including ARAF, BRAF, NRAS, HRAS, KRAS, PTPN11, CBL, SOS1, RIT1, RASA1, and SHOC2 (42, 77–88). Here, CBL is linked to lymphedema.