IPO8 encodes importin 8, a nuclear transport receptor that mediates the import of proteins into the nucleus through a Ran-dependent mechanism. The protein can function autonomously or associate with importin-beta (KPNB1) to recognize nuclear localization signals and facilitate translocation through the nuclear pore complex. Beyond its canonical role in nuclear protein import, IPO8 mediates cytoplasm-to-nucleus shuttling of diverse cargo proteins including the signal recognition particle protein SRP19, Argonaute-microRNA complexes, the transcription factors JUN and NF-κB p65, the translation initiation factor EIF4E, and SMAD proteins activated downstream of transforming growth factor-beta and bone morphogenetic protein signaling pathways. Clinically, IPO8 variants are associated with developmental disorders. Patients carrying IPO8 bi-allelic loss-of-function mutations present with early-onset thoracic aortic aneurysm and connective tissue abnormalities including arachnodactyly, joint hypermobility, facial dysmorphisms, and motor developmental delay 1. Additionally, IPO8 expression is elevated in inflammatory contexts: expression increases proportionally with periodontitis severity 2 and is upregulated in inflamed dental pulps 3, where it contributes to NF-κB activation and inflammatory cytokine production. Knockdown of IPO8 attenuates lipopolysaccharide-induced NF-κB signaling in macrophages 2, suggesting that IPO8 inhibition may represent a therapeutic approach for managing periodontal and pulpal inflammation.