Pathologies at the gateway: exploring the link between nucleoporins and inherited diseases

Abstract Nuclear pore complexes serve as essential gatekeepers of the nuclear envelope, playing crucial roles in regulating transport across the nuclear envelope and maintaining compartmentalization between the nucleus and cytoplasm. While they are fundamental to all nucleated cells, the nucleoporins that make up these complexes are associated with various inherited diseases, often affecting specific cells, tissues, or organs. In this overview, we describe the clinical features, summarize genotype-phenotype correlations at the level of individual genes and specific alleles, and relate this information to insights from cellular biology regarding nucleoporins to illuminate potential disease mechanisms. Our aim is to include significant clinical perspectives that are frequently overlooked in standard cell biology reviews, while ensuring accessibility for readers without a medical background. At the same time, we hope to provide valuable insights for geneticists and clinicians interested in the discussed pathologies, but may have limited background in molecular cell biology. Summary statement Mutations in nucleoporin-encoding genes, the proteins that form nuclear pore complexes, are associated with various hereditary diseases. We summarize our emerging knowledge to connect clinical manifestations with insights from cell biology.