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Nucleocytoplasmic trafficking describes the process whereby molecules destined for the nucleoplasm or cytoplasm move across the nuclear envelope. This transport regulates transcription and translation by respective control of transnuclear movements of transcription factors and messenger RNA. Transport across the nuclear envelope occurs through large MDa pores embedded in the inner and outer nuclear membranes, and is a dynamic, adaptable process modulated by biochemical and biophysical cellular milieus. The present review discusses current understanding of the composition and function of the nuclear pore complex through which transport occurs; regulatory elements within molecular cargo that influence its movement into and out of the nucleus; transport associated proteins that guide the cargo across the nuclear envelope; and factors responsible for modulating nucleocytoplasmic transport.