Constitutive activation of the MAPK signaling pathway via a mutation in BRAF (V600E) increases phosphorylation of FAM129B and mediates its cytosolic localization. In turn, FAM129B binds to KEAP1, preventing association between KEAP1 and NRF2, thus NRF2 protein accumulates, translocates to the nucleus, and activates transcription of its target genes.