Rho GDP-dissociation inhibitor 1

Rho GDP-dissociation inhibitor 1 (Rho GDI 1), encoded by ARHGDIA, is a regulatory protein that controls Rho GTPase homeostasis (UniProt: P52565). It inhibits GDP dissociation from Rho proteins including CDC42, RAC1, and RHOA, maintaining them in an inactive cytosolic state and protecting them from degradation. The protein also mediates extraction of both inactive and activated Rho GTPases from membranes, thereby regulating their recycling and distribution. Through modulation of Rho signaling, it influences cell motility and has been shown to inhibit migration and invasion in glioma cells.

Rho GDI 1 is associated with Nephrotic syndrome 8, a kidney disease characterized by progressive renal failure and proteinuria (UniProt: P52565). The protein's regulation of Rho GTPases implicates it in broader cytoskeletal and signaling processes relevant to multiple tissues.

In Alzheimer's disease, Rho GDI 1 is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log₂FC of −0.31 across analyzed subcellular fractions (Chaparral AD proteomics). This reduction in a key regulator of Rho GTPase signaling may contribute to aberrant cytoskeletal dynamics associated with neurodegeneration.