Transport of proteins and nucleic acids between the nucleus and the cytoplasm is essential for virtually all cellular functions. The nuclear pore complexes (NPCs), large assemblies composed of more than 1000 individual nucleoporins, control the bidirectional translocation of these macromolecules. NPCs are anchored in the nuclear membrane by a small set of nucleoporins (TM-Nups) containing one or more transmembrane domains. Using a novel proteomics approach (James et al., 2022; Rodriguez-Gonzalez et al., 2026), we recently identified a novel TM-Nup, TMEM209, as an integral component of the NPC (Kohlhause et al., 2026). All five TM-Nups identified so far appear to be non-essential at the singlecell level, reflecting the dynamics and redundancy of these proteins. In contrast, about 20 distinct soluble nuclear transport receptors interact with their cargo molecules and mediate their import or export through the NPC (Baade and Kehlenbach, 2019). The focus of the presentation will be on the major nuclear export receptor CRM1/Xpo1, a member of a larger family of proteins that also mediate nuclear import (Kehlenbach et al., 1998). CRM1 exports hundreds of proteins containing a characteristic nuclear export sequence (NES) and also several RNA species (Kehlenbach and Chook, 2025; Thakar et al., 2013). Beyond its established role in nuclear export, CRM1 participates in the biogenesis of the NPC (Hamed et al., 2021) and in import of viral genomes into the nucleus (Carlon-Andres et al., 2020; Lagadec et al., 2021).