GLE1 is a nuclear export factor essential for mRNA transport and gene expression regulation. Primary Function: GLE1 mediates the export of polyadenylated mRNAs from the nucleus through nuclear pore complexes (NPCs) into the cytoplasm, functioning at the critical terminal step of mRNA transport 1. Mechanism: GLE1 works in conjunction with inositol hexakisphosphate (IP6) to spatially regulate DEAD-box protein Dbp5 (human DDX19B) at the NPC cytoplasmic face, enabling mRNP remodeling during export 23. GLE1 also binds the nucleoporin Nup42, which is integral to Dbp5 activation 3. Beyond mRNA export, GLE1 regulates multiple gene expression steps including transcription, translation initiation, translation termination, and stress granule formation, with functions governed by phosphorylation-dependent oligomerization 45. Disease Relevance: Mutations in GLE1 cause lethal congenital contracture syndrome 1 (LCCS-1) and lethal arthrogryposis with anterior horn cell disease (LAAHD), with disease variants disrupting NPC localization and mRNA export function 1. In vivo modeling demonstrates that LCCS-1-associated mutations impair stress granule assembly, RNA/protein synthesis, and neural crest development, leading to motor neuron defects and early lethality 6. Clinical Significance: GLE1 mutations associate with congenital arthrogryposis and anterior horn cell degeneration, representing severe developmental disorders affecting neuromuscular development 7.