PLEKHG2 and the PLEKHG family: Linking Rho family GTPases to neural development and disorders.

Rho family small GTPases (Rho GTPases) are key regulators of cellular morphology, primarily through their control of the actin cytoskeleton. They play crucial roles in various cellular processes, including cell division, adhesion, and migration. The activity of Rho GTPases is tightly regulated by specific guanine nucleotide exchange factors (GEFs), which facilitate the exchange of GDP for GTP, thereby activating the GTPases. In the human genome, RhoGEFs are categorized into two major families: the DOCK family, comprising 11 members characterized by dedicator of cytokinesis (DOCK) homology regions, and the Dbl family, consisting of 64 members that contain a diffuse B-cell lymphoma (Dbl) homology domain. This review focuses on the pleckstrin homology and RhoGEF domain containing G (PLEKHG) family within the Dbl family of RhoGEFs, which remains largely uncharacterized. We summarize their structure and function, with a particular emphasis on PLEKHG2, discussing its regulatory mechanisms, interactions with various molecules, and its involvement in neural functions.