XPO6 (exportin 6) mediates nuclear export of actin and profilin-actin complexes in somatic cells 1. In normal epithelial cells, laminin-111 signaling attenuates PI3K pathway activity, upregulating XPO6 to facilitate actin export and promote cellular quiescence 1. XPO6 activity is regulated by RASSF1A at the nuclear envelope, which supports XPO6 binding to RAN GTPase and maintains nuclear actin homeostasis; loss of RASSF1A in cancer cells disrupts this pathway and impairs MRTF-A/SRF-dependent transcription 2. Beyond actin transport, XPO6 exports TLR2 mRNA in pulmonary monocytes, facilitating TLR2 protein expression and MyD88/NF-κB inflammatory signaling in COPD 3, and mediates HSV-1 glycoprotein M nuclear release 4. Clinically, XPO6 upregulation is a cancer driver event. Elevated XPO6 expression associates with poor prognosis and rapid prostate cancer recurrence in low-risk patients 5, and correlates with metastatic potential and advanced Gleason grades 6. In breast cancer, XPO6 upregulation drives tumorigenesis by exporting nuclear profilin-1, preventing its interaction with the super elongation complex and repression of MYC and other pro-cancer genes 7. XPO6 inhibition represents a therapeutic opportunity, potentially sensitizing cancer cells to BET inhibitors.