Proteins transported into and out of the nucleus require amino acid motifs called NLSs and NESs, respectively. The amino acid sequences of these signals vary considerably. A superfamily of transport receptors has been identified and each member contains three transport-related domains. Transport receptors bind to the signal sequences, either directly or through adapter proteins, to promote nucleocytoplasmic transport. The diversity of signals, receptors and adapter proteins suggests that there are many pathways for nuclear entry or exit. The direction of transport (into or out of the nucleus) is regulated in part by the small GTPase Ran as well as by intrinsic substrate motifs.