Arhgdib, also known as Rho GDP-dissociation inhibitor 2 (RhoGDI2), is a negative regulator of the Rho guanosine triphosphate (RhoGTP)ases RhoA, Rac1, and Cdc42. Its main function is regulating the actin network in a variety of cells. The protein is mainly expressed intracellularly, with some expression on the cell surface [4].

In bladder cancer, KDM6A promotes the transcription of Arhgdib by demethylating histone H3 lysine di/trimethylation (H3K27me2/3), which consequently leads to the inhibition of Rac1 and blocks metastasis [1]. In breast cancer, Arhgdib expression is significantly higher in cancer tissues compared to benign tissues, positively correlated with tumor size, lymph node metastasis, and TNM stage. Depletion of Arhgdib decreased the proliferation, migration, and invasion of breast cancer cells [5]. In glioma, Arhgdib is overexpressed and correlates with poor patient prognosis. It is involved in the recruitment of immunosuppressive cells, such as M2 macrophages and neutrophils, contributing to the alteration of the glioma immunosuppressive microenvironment [6]. In trophoblasts, PD-L1 enhances migration and invasion by upregulating Arhgdib via transcription factor PU.1 [7]. Also, in kidney transplantation, pre-transplant anti-Arhgdib antibodies are associated with long-term kidney graft loss, and the presence of these antibodies has an additive effect in patients with donor-specific anti-HLA antibodies on the risk of graft failure [2,3].

In summary, Arhgdib plays crucial roles in multiple biological processes and diseases. In cancer, it is involved in processes like metastasis, proliferation, and invasion, as well as in modulating the tumor microenvironment. In kidney transplantation, antibodies against Arhgdib are associated with graft outcomes. Understanding Arhgdib's functions can potentially lead to new diagnostic and therapeutic strategies for related diseases [1,2,3,5,6,7].