Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.

Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are structurally related and freely move across the nucleus by facilitated diffusion. Upon cargo binding, the cargo-receptor complex docks onto the nuclear pore complex or NPC embedded on the nuclear membrane.

Two models describe docking and movement of the cargo-receptor complex across the NPC as follows:

1. The Brownian affinity gating model suggests a random movement of the receptor-cargo complex across the NPC. The receptor-cargo complex selectively interacts with the nucleoporins lining the NPC to form transient bonds and facilitate their movement.
2. The selective phase model suggests unstructured phenylalanine and glycine repeats called FG repeats on the inner channel of the NPC form gel-like matrices. Transient interactions with FG repeats help dissolve the matrix gel phase as the receptor-cargo move through the pore.

On the nuclear side, a small GTPase Ran, bound to GTP to the incoming cargo-importin complex, induces a conformational change in importin beta and cargo delivery inside the nucleus.

During nuclear export, Ran-GTP inside the nucleus associates with exportin to form the cargo-export complex and move to the cytosol. Ran-GTP hydrolysis on the cytoplasmic fibrils of NPC dissociates the cargo and receptor, releasing them into the cytosol.