During the last years, efforts of many laboratories have led to delineate the importance of ERK5 in controlling cell proliferation in normal and cancer cells, by mechanisms that are both dependent and independent of its kinase activity: nuclear ERK5 activates transcription factors by either direct phosphorylation or acting as co-activator thanks to a unique transcriptional activation domain located at its C-terminal tail. The gene discussed is MAPK7; the disease is cancer.