ARHGDIB (Rho GDP dissociation inhibitor beta) is a molecular regulator of Rho family GTPases that inhibits GDP dissociation and prevents GTP binding, thereby suppressing Rho protein activation and controlling actin cytoskeleton reorganization. In bladder cancer, ARHGDIB functions as a tumor suppressor: the KDM6A-ARHGDIB axis restrains cell motility and invasiveness by inhibiting Rac1 1, while lysine lactylation of ARHGDIB at positions K47 and K50 stabilizes this tumor-suppressive function; HDAC2-mediated delactylation abrogates tumor suppression and promotes metastasis and cisplatin resistance, which can be reversed by HDAC inhibitors such as entinostat 2. In breast cancer, elevated ARHGDIB expression correlates with poor prognosis and associates with increased tumor size, lymph node metastasis, and TNM stage, with downstream effects on epithelial-mesenchymal transition mediated through MMP2 3. In glioma, ARHGDIB is markedly overexpressed and promotes an immunosuppressive microenvironment by recruiting M2 macrophages and neutrophils, serving as a prognostic biomarker for adverse outcomes 4. ARHGDIB also appears in diagnostic models for sepsis-induced acute lung injury as one of five consensus biomarkers 5, and in kidney transplantation, anti-ARHGDIB autoantibodies associate with antibody-mediated rejection and allograft failure 6, with an additive risk when combined with donor-specific HLA antibodies. Recent evidence suggests circSipa1l1 regulates melanoma differentiation through the IGF2BP1-ARHGDIB-ERK axis 7, and PD-L1 modulates trophoblast migration partly via PU.1-regulated ARHGDIB expression 8.