Ran GTPase-activating protein 1

RANGAP1 (Ran GTPase-activating protein 1) is a 587-amino acid cytoplasmic enzyme that catalyzes GTP hydrolysis on the RAN small GTPase, converting active GTP-bound RAN to its inactive GDP-bound form (UniProt: P46060). This activity is essential for RAN-mediated nuclear-cytoplasmic transport, including the dissociation of cargo from nuclear export complexes after RAN-XPO1-RANBP2-mediated export.

RANGAP1 functions centrally in nucleocytoplasmic transport pathways. No baseline disease associations are documented in UniProt, but the protein's role in nuclear import and export processes positions it at the intersection of nuclear function and cellular stress responses.

In Alzheimer's Disease, RANGAP1 is significantly upregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change: +0.2041; Chaparral AD proteomics). This upregulation was detected via TMT-labeled quantitative proteomics across subcellular fractions from human AD brain samples, suggesting that altered nuclear transport capacity or RAN GTPase regulation may be engaged in AD pathology.