Going out of the brain: Non-nervous system physiological and pathological functions of Cdk5

► In this review we analyze the state-of-art of Cdk5 signaling outside the nervous system. ► We described novel roles for Cdk5 in transcription, translation and cell cycle regulation. ► We report the pathological roles for Cdk5 in cancer, senescence, muscular dystrophy and diabetes. ► Alternative isoform functions are described. ► We envision novel roles for the Cdk5 kinase in territories outside the nervous system.