ARHGDIG (Rho GDP dissociation inhibitor gamma, also called RhoGDI3) is a GDP dissociation inhibitor that regulates Rho GTPase signaling with tissue-specific expression patterns. Structurally, the gene spans over 4 kb with six exons and five introns, located at chromosome 16.3 1. ARHGDIG shows preferential expression in brain and pancreas, with lower levels in kidney and other tissues 12. Functionally, ARHGDIG binds to and inhibits GDP/GTP exchange of Rho proteins, particularly RhoB, maintaining them in an inactive cytosolic state 2. The protein localizes to cytoplasmic vesicles and the trans-Golgi network, where it can modulate protein compartmentalization 23. Disease relevance includes vascular pathology, where ARHGDIG participates in NLRP3 inflammasome activation and vascular smooth muscle cell phenotypic modulation, contributing to neointima formation following balloon injury 3. In hepatocellular carcinoma, sorafenib-induced ARHGDIG upregulation triggers IL4 secretion, leading to macrophage extracellular trap formation that inhibits ferroptosis and promotes drug resistance 4. Additionally, ARHGDIG promoter methylation is associated with clear-cell renal cell carcinoma risk, particularly modifying dietary sodium intake associations 5. The gene's chr16 location at 16p13.3 places it in a region prone to deletions associated with multiple genetic diseases 16.