ARHGDIB (Rho GDP dissociation inhibitor beta) is a cytosolic protein that regulates Rho family GTPase signaling by inhibiting GDP dissociation and GTP binding 12, thereby controlling actin cytoskeleton reorganization 3. Beyond its canonical GTPase regulatory function, ARHGDIB exhibits diverse roles across multiple pathological contexts. In bladder cancer, the FOXA1-KDM6A-ARHGDIB axis suppresses metastasis by inhibiting Rac1 activation 4, while ARHGDIB delactylation by HDAC2 promotes metastasis and cisplatin resistance through impaired Rac1 binding 5. In glioma, elevated ARHGDIB expression correlates with poor prognosis and recruits immunosuppressive M2 macrophages, reshaping the tumor microenvironment 6. In melanoma, the circSipa1l1-IGF2BP1-ARHGDIB axis regulates cell differentiation via ERK signaling 7. Clinically, anti-ARHGDIB autoantibodies associate with kidney allograft rejection; combined presence with donor-specific HLA antibodies increases graft failure risk 19.5-fold 89. ARHGDIB also emerged as a diagnostic biomarker for sepsis-induced acute lung injury 10. These findings establish ARHGDIB as a multifunctional regulator with significant implications for cancer progression, transplant immunity, and acute inflammatory conditions.