Aberrations in the reactivated MAPK pathway, such as genetic alterations of RAS (Nazarian et al, 2010) and MEK (Emery et al, 2009), BRAF amplification (Shi et al, 2012), loss of NF1 (Whittaker et al, 2013), deregulation of COT1 (Johannessen et al, 2010), and BRAF alternative splicing (Poulikakos et al, 2011), are frequently detected in melanoma progression despite treatment (Shi et al, 2014b). The gene discussed is MAP2K7; the disease is melanoma.