ARHGEF37 is a Rho guanine nucleotide exchange factor that functions as a regulatory protein in clathrin-mediated endocytosis (CME). Structurally, ARHGEF37 contains a unique BAR domain and exhibits phosphatidylinositol 4,5-bisphosphate-dependent protein-membrane interactions 1. Mechanistically, ARHGEF37 accumulates at dynamin 2-rich late endocytic sites and enhances endocytosis rates, suggesting a role in fine-tuning the late stages of CME 1. Beyond endocytosis, ARHGEF37 functions as a direct activator of the small GTPase Cdc42, which promotes invadopodia formation and trans-endothelial migration in hepatocellular carcinoma (HCC) cells 2. Clinically, ARHGEF37 overexpression is associated with poor prognosis in HCC, correlating with tumor invasiveness, pulmonary metastasis, and advanced disease stage 2, 3. Additionally, elevated ARHGEF37 expression has been identified in benign prostatic hyperplasia and correlates with MAPK pathway dysregulation 4. Pharmacologically, Cdc42 inhibition with ZCL278 suppresses ARHGEF37-mediated HCC metastasis in vivo 2, identifying the ARHGEF37/Cdc42 axis as a potential therapeutic target for cancer progression.