The nuclear pore complex is a large multiprotein complex traversing the nuclear envelope. Many of its components harbor intrinsically disordered regions that undergo spontaneous condensation. Here, we discuss how assembly factors may guide their condensation, which must be carefully coordinated in space and time. We further discuss how defects in this process contribute to human pathologies, focusing on neurological disorders.

The nuclear pore complex (NPC) is among the most elaborate protein complexes in eukaryotes. While ribosomes and proteasomes are known to require dedicated assembly machinery, our understanding of NPC assembly is at a relatively early stage. Defects in NPC assembly or homeostasis are tied to movement disorders, including dystonia and amyotrophic lateral sclerosis (ALS), as well as aging, requiring a better understanding of these processes to enable therapeutic intervention. Here, we discuss recent progress in the understanding of NPC assembly and highlight how related defects in human disorders can shed light on NPC biogenesis. We propose that the condensation of phenylalanine-glycine repeat nucleoporins needs to be carefully controlled during NPC assembly to prevent aberrant condensation, aggregation, or amyloid formation.