RAN and Hutchinson-Gilford progeria syndrome: Many reports have indicated that disruption of the Ran gradient leads to impairment of importin-β-dependent cargo import, but it has been shown that disruption of the Ran gradient in Hutchinson-Gilford Progeria syndrome (HGPS) fibroblasts did not affect transport of the classical SV40 NLS-cargo protein, despite its alteration of the transport of the Tpr protein, which has bipartite NLS21,36.