Mutations in nucleoporins and their roles in human diseases: Integrating evidence on specific NUP functions

Nuclear pore complexes (NPCs), massive assemblies of approximately 30 distinct nucleoporins (NUPs), serve as the major gateways for nucleocytoplasmic transport. Recent research highlights that NUP aberrations-ranging from gene fusions and mutations to pathological protein accumulation-are increasingly implicated in the pathogenesis of a broad spectrum of human diseases. The underlying pathogenic mechanisms are highly multifactorial, encompassing the structural collapse of the NPC, transport network paralysis, epigenetic hijacking via liquid-liquid phase separation, and off-pore transcriptional dysregulation. This review synthesizes the multifaceted molecular etiology of NUP-associated pathologies. A deeper understanding of these diverse functions will shed light on the broader biological roles of NUPs and guide future research into targeted and personalized therapeutic strategies for NUP-associated disorders.