Activating MAPK pathway mutations in LCH. (A) Physiologic MAPK signaling transduces extracellular signal through receptor tyrosine kinase (RTK), which activates RAS, then RAF, then MEK, then ERK proteins, which in turn regulate cell-specific nuclear targets and gene transcription programs. (B) Activating mutations in LCH such as BRAFV600E drive constitutive ERK activation and downstream transcriptional targets including increased transcription of BCL2L1 and decreased CCR7.