Ras accumulates in the active GTP-bound conformation in response to growth factor stimulation and other extracellular stimuli. Normal Raf proteins bind to Ras-GTP and signal as homo- and heterodimers. BRAF and ARAF mutations found in LCH and other cancers exhibit constitutive kinase activation, which results in the sequential activation of MEK and ERK. Vemurafenib and trametinib are potent and selective inhibitors of Raf and MEK, respectively.