YAP nuclear-cytoplasmic translocation is regulated by mechanical signaling, protein modification, and metabolism.

Nuclear-cytoplasmic transport is necessary for the biological function of nuclear proteins. The mechanism underlying this process is very complex and has been a subject of intense research. Yes-associated protein (YAP), a Hippo signaling pathway effector, localizes to both the cytoplasm and the nucleus and can influence cell proliferation, stem cell status, and tissue homeostasis. Recent studies have focused on the significance of YAP distribution between the nucleus and the cytoplasm in disease, but it remains unclear how this dynamic process is regulated. In this review, we discuss YAP nuclear-cytoplasmic transport under different physiological and pathological conditions in terms of mechanical signaling, protein modification, and metabolism. Understanding the mechanisms underlying nuclear-cytoplasmic YAP transport mechanism under different physiological and pathological conditions may help identify important targets for disease treatment.