PLEKHG5 (Pleckstrin homology domain containing, family G member 5) is a guanine nucleotide exchange factor that activates RHOA, influencing cell polarization. It also promotes tight junction stabilization and plays a role in angiogenesis through regulation of endothelial cells chemotaxis. In the nervous system, PLEKHG5 is involved in the control of neuronal cell differentiation, and mutations in the gene lead to lower motor neuron disease (LMND) and Charcot-Marie-Tooth disease (CMT). In immunohistochemistry of normal tissue, PLEKHG5 has nuclear and cytoplasmic positivity in neuronal and glial cells throughout the brain, and is also present in most other tissues throughout the body. References: The UniProt Consortium. Nucleic Acids Res. 47: D506-515 (2019); Nucleic Acids Res. 2016 Jan 4;44(D1):D733-45, PMID:26553804; Orphanet J Rare Dis. 2013; 8: 104, PMID: 23844677;