Pleckstrin homology domain-containing family G member 5 (PLEKHG5)

Pleckstrin homology domain-containing family G member 5 (PLEKHG5) is a **guanine nucleotide exchange factor (GEF)** specific for Rho family GTPases, especially RhoA, encoded by the *PLEKHG5* gene in humans[1][2][3]. PLEKHG5 contains Dbl homology (DH) and pleckstrin homology (PH) domains and catalyzes the exchange of GDP for GTP on RhoA, thereby activating signaling cascades controlling actin cytoskeleton dynamics and cell polarity[1][3]. It plays a key role in regulating **cell polarization, apical cell constriction**, and tight junction formation, as well as activating NF-kappaB signaling[1][3]. Mutations in *PLEKHG5* are causative for **distal spinal muscular atrophy type 4 (DSMA4)**, and its overexpression has been linked to increased invasiveness in gliomas[1]. The self-association of PLEKHG5, mediated via its PH domain, is essential for its function in apical constriction and probably in its physiological roles[2][3]. There are currently no known drugs that directly target PLEKHG5, but its activity is of interest in the context of neurodegenerative disease and cancer biology.

Other names

KIAA0720PH domain-containing family G member 5GEF720SyxTechARHGEF45synectin-binding guanine exchange factorCMTRICDSMA4HMNR4NFkB activating protein

Drugs would be expected to modulate guanine nucleotide exchange activity on RhoA or modulate pleckstrin homology (PH) domain–mediated protein interactions. No direct clinical inhibitors/activators reported.