The presence of a C-terminal TAD that can integrate signals from both the ERK5 kinase domain and non-ERK5 kinases, including ERK1/2, to direct nuclear entry of ERK5 may have important implications for ERK5 signalling in tumours cells with deregulated ERK1/2 signalling and their response to therapeutics (Figure 1). Here, MAPK3 is linked to neoplasm.