RANBP3 (RAN binding protein 3) functions as a multifaceted nuclear cofactor that regulates nucleocytoplasmic transport and cellular signaling pathways. As a primary function, RANBP3 acts as a scaffolding protein that enhances CRM1-mediated nuclear export by stabilizing CRM1-cargo interactions and promoting export complex assembly 1. The protein binds directly to CRM1 and forms trimeric complexes with CRM1 and RanGTP, stimulating CRM1-dependent protein export in permeabilized cells 1. Mechanistically, RANBP3 associates with the Ran-specific guanine nucleotide exchange factor RCC1, increasing its catalytic activity and serving as a scaffold to promote efficient assembly of export complexes 2. RANBP3 plays a crucial role in TGF-β signaling termination by directly recognizing dephosphorylated Smad2/3 and mediating their nuclear export in a Ran-dependent manner 3. The protein's activity is regulated by phosphorylation at Ser58, with PPM1A dephosphorylation promoting its export capacity 4. In disease contexts, RANBP3 functions as a tumor suppressor in colorectal cancer, promoting nuclear export of β-catenin to inhibit oncogenic Wnt signaling 5, and reduced RANBP3 expression is associated with male infertility and spermatogenesis disorders 6.