A. Depiction of the basic structure of the NPC. Cytoplasmic filaments and the nuclear basket extend into the cytoplasm and nucleoplasm respectively, while transmembrane Nups anchor the NPC to the nuclear envelope. The central channel is rich in FG-Nups, that form a selectivity filter to prevent the unregulated passage of large proteins (i.e. ~>40kDa) though the pore. The LINC complex is tightly associated with the nuclear pore and connects the nuclear lamina with the cytoskeleton. B. Representation of the NCT pathway. Importins bind to their cargo and facilitate movement through the NPC. In the nucleoplasm, Ran-GTP either binds to importins to trigger the release of the cargo, or to the exportin-cargo complex, facilitating its transport through the nuclear pore to the cytoplasm. RanGAP1 then hydrolyzes Ran-GTP to Ran-GDP and triggers the release of the cargo into the cytoplasm. RCC1 restores the GTP-bound state of Ran in the nucleoplasm, resetting the cycle.