Ran is a small GTP-binding protein. The name is an acronym for ‘Ras-like nuclear GTPase’; it was also once known as TC4. Ran, the epic war movie by Akira Kurosawa; Ran, the alien girl in the Japanese anime series Urusei Yatsura; the Rainforest Action Network. When it was found to be an essential factor in nucleocytoplasmic protein import. It was later implicated in nuclear protein export and RNA transport, and provided a key to unlock the mechanisms of these processes. Yes, as you ask. When Ran was first identified, there were tantalizing hints that it is also involved in the cell cycle, and the heretics who had held fast to this belief were finally vindicated by the discovery that Ran plays a critical part in the formation of mitotic spindles. Cargo is transported through pores in the nuclear envelope, in association with carriers that bind to pore proteins called nucleoporins. A Ran–GTP gradient across the envelope is created by the asymmetric distribution of the GTPase activating protein known as RanGAP, which is in the cytosol, and of the guanine nucleotide exchange factor RanGEF in the nucleus. Ran–GTP triggers release of imported cargo from import carriers, but promotes loading of export cargo onto export carriers. So, import cargo is dumped in the nucleoplasm and export cargo is collected (see Figure). The reverse happens in the cytoplasm, where RanGAP stimulates hydrolysis of the GTP on Ran bound to the carriers. Yes. Import carriers recycle back to the cytoplasm bound to Ran–GTP, which needs to be removed for the next cycle of import. Export carriers bring both Ran–GTP and cargo to the cytoplasm, and presumably recycle back into the nucleus alone. That is the job of a small factor called NTF2 (or p10). It binds to Ran–GDP and carries the Ran through the nuclear pores into the nucleus where it is released by RanGEF, which converts Ran to the GTP-bound state. NTF2 then cycles back to the cytoplasm to pick up more Ran–GDP. They have been called importins, exportins, transportins, karyopherins and Kaps, among other things. There are currently thought to be about 23 carriers in mammals and 14 in budding yeast. There are also adaptor proteins that link specific cargoes to their carriers. Don’t ask. But a move is under way to name them all ‘schleppins’. Personally, we can’t see it catching on. In the meantime, how about ‘karyopherins’ for the entire class of carriers, ‘importins’ for those that import, ‘exportins’ for those that export and ‘transportins’ for those that do both? In your dreams — only the simple stuff is at all clear. There are a lot of accessory proteins that we don’t understand (such as RanBP3/Yrb2, Nxt1 and Mog1), and different classes of carrier (such as TAP/Mex67), and neither the interactions of carriers with the pores nor the translocation mechanism is really understood. There are also questions about cargo specificity and Ran-independent transport mechanisms to be explored. The latest idea is that RanGEF bound to chromatin produces a sort of Ran–GTP atmosphere close to the chromatin surface. This atmosphere may tell the cell where the chromatin is, and control mitotic spindle formation and nuclear envelope assembly, in addition to marking the nuclear compartment in interphase cells. Maybe. Novartis is interested in an antifungal agent called leptomycin B, which specifically inhibits the export receptor Crm1. Many viruses need to get into the nucleus to replicate, so drugs that block certain nuclear transport processes might just find therapeutic use as antiviral agents. Gorlich D, Kutay U: Transport between the cell nucleus and the cytoplasm.Annu Rev Cell Dev Biol 1999, 15:607-660. Kaffman A, O'Shea EK: Regulation of nuclear localization: a key to a door.Annu Rev Cell Dev Biol 1999, 15:291-339. Melchior F, Gerace L: Two-way trafficking with Ran.Trends Cell Biol 1998, 8:175-179. Nakielny S, Dreyfuss G: Transport of proteins and RNAs in and out of the nucleus.Cell 1999, 99:677-690.