RANGAP1 is a GTPase-activating protein that converts RAN-GTP to RAN-GDP in the cytoplasm, a critical step for nuclear-cytoplasmic transport 1. By promoting RAN-GDP formation, RANGAP1 mediates cargo dissociation from nuclear export complexes containing XPO1 and RANBP2, facilitating both nuclear import and export 2. Beyond canonical nucleocytoplasmic transport, RANGAP1 localizes to kinetochores during mitosis, where it recruits protein phosphatase 1-γ to regulate the spindle assembly checkpoint and prevent TOP2A degradation, thereby maintaining chr22 decatenation and chromosome 22 3. RANGAP1 is subject to SUMOylation, generating SUMO-dependent protein interactions 4. Functionally, RANGAP1 loss causes chromosome 22 and chr22, driving rapid osteosarcoma tumorigenesis 3. Disease relevance extends to neurodegeneration: C9orf72 repeat expansion RNA mislocalizes RANGAP1, impairing nucleocytoplasmic transport and contributing to amyotrophic lateral sclerosis pathogenesis 5. Additionally, cytoplasmic TDP-43 aggregation induces RANGAP1 mislocalization, inhibiting nuclear import and triggering cell death 6. Clinically, RANGAP1 function impacts calcific aortic valve disease through its interaction with palmdelphin, affecting nuclear localization of p53/p21 and nuclear resilience to mechanical stress 7. RANGAP1 also participates in RAS-dependent oncogenic nuclear protein export independent of canonical RAS signaling 8.