ARHGEF11 encodes PDZ-RhoGEF, a guanine nucleotide exchange factor that primarily activates RhoA GTPase 1 and can be activated by Gα12/13 signaling 2. The protein localizes to dendritic spines and synaptic membranes 1, where it regulates actin cytoskeleton dynamics and dendritic morphogenesis 1. ARHGEF11 is enriched in the prefrontal cortex and represents a convergence point for cognition-relevant signaling cascades controlled by miR-132 and DISC1 3. Mechanistically, ARHGEF11 regulates insulin signaling in placenta and may suppress insulin pathway components, contributing to fetal macrosomia in normal glucose tolerance pregnancies 4. In cancer, ARHGEF11 is upregulated in hepatocellular carcinoma, where it promotes proliferation and epithelial-mesenchymal transition via β-catenin pathway activation, correlating with poor prognosis 5. Additionally, oncogenic Gαq enables ARHGEF11 to activate RhoJ, promoting endothelial cell responses relevant to tumor angiogenesis 6. Genetically, ARHGEF11 variants associate with type 2 diabetes risk through insulin resistance mechanisms 7 and with schizophrenia susceptibility in Japanese populations via specific haplotypes 8. During vertebrate development, ARHGEF11 is essential for proper ciliated epithelial formation and laterality determination 2.