The Power of Nup85: Controlling Molecular Traffic and Cellular Fate

Nucleocytoplasmic transport is a fundamental process that maintains cellular homeostasis, mediated by the nuclear pore complex (NPC), a highly organized macromolecular assembly embedded in the nuclear envelope (NE). Among its structural components, nucleoporin 85 (Nup85) is a core element of the evolutionarily conserved Nup107-160 (Y-) complex, where it plays a central role in maintaining NPC architecture and function. This review provides a comprehensive overview of current knowledge on Nup85, integrating its structural organization, molecular interactions, and functional roles across diverse eukaryotic systems. Nup85 is characterized by an α-helical solenoid architecture within the ancestral coatomer element (ACE1) family and forms critical interactions with multiple nucleoporins, including Seh1, Nup43, Nup120, and Sec13, thereby contributing to NPC assembly and stability. Furthermore, Nup85 extends beyond a scaffolding role to regulate mRNA export, nucleocytoplasmic transport, gene expression, and cell cycle progression. Studies across model organisms highlight its conserved roles in processes such as stress signaling, development, mitosis, and metabolic regulation. Importantly, dysregulation or mutation of Nup85 has been associated with a range of human pathologies, including kidney disease, neurodevelopmental disorders, cancer progression, inflammatory conditions, and infectious diseases. This review aims to identify key gaps in the current understanding of Nup85, highlight its importance, and provide a basis for future research directions.