NET1 (Neuroepithelial cell-transforming gene 1, Net1A, ARHGEF8) is a guanine nucleotide exchange factor protein that activates RhoA GTPase. Studies in zebrafish have illustrated that NET1 is important for embryogenesis and in establishing the body plan. Furthermore, variants in NET1 are associated with oppositional defiant disorder (ODD) and attention-deficit/hyperactivity disorder (ADHD) in humans. In cancer, deletion mutations in NET1 cause the protein to be re-localized to the cytosol, where it aberrantly activates RhoA and induces transformation. In immunohistochemistry, NET1 has cytoplasmic positivity in the brain, gastrointestinal tract, muscle, reproductive tissues, kidney, liver and some immune tissues. References: J Child Psychol Psychiatry. 2015 Jan;56(1):58-66, PMID: 24942521; Zhonghua Yi Xue Za Zhi. 2015 Nov 3;95(41):3351-6, PMID: 26812975; Cell Res. 2017 Feb; 27(2): 202–225, PMID: 27910850; Mol Cell Biol. 2007 Dec; 27(24): 8683–8697, PMID: 17938206; Journal of Cell Science 2018 131: jcs204644, DOI: 10.1242/jcs.204644