TNPO1 (transportin 1) is a nuclear import receptor that mediates transport of cargo proteins into the nucleus through recognition of nuclear localization signals (NLS). Beyond canonical nuclear import, TNPO1 functions as a molecular chaperone that suppresses pathological phase separation of RNA-binding proteins (RBPs) with prion-like domains, including FUS, TDP-43, hnRNPA1, and hnRNPA2 1. TNPO1 recognizes both classical PY-NLS motifs and nonclassical RG/RGG-rich regions in cargo proteins 2, with arginine methylation regulating FUS-TNPO1 interactions 3. Beyond nuclear import, TNPO1 serves as a ciliary transport adaptor, binding the RVEP motif of Arl13b to facilitate its ciliary localization in cooperation with Rab8 4. Dysregulation of TNPO1 has disease relevance: mutations weakening TNPO1-FUS binding cause amyotrophic lateral sclerosis (ALS), while TNPO1 aggregation contributes to frontotemporal dementia (FTD) pathology 3. In esophageal cancer, the circBCAR3-miR-27a-3p axis upregulates TNPO1, promoting tumorigenesis and metastasis 5. Additionally, sphingosine directly binds TNPO1 to inhibit nuclear import while activating PP2A, suggesting therapeutic potential in cancer 6.