ARHGEF17 is a guanine nucleotide exchange factor (GEF) that activates Rho-family GTPases (RhoA, RhoB, RhoC) through its Dbl homology domain, thereby regulating actin cytoskeleton organization and cell morphology 1. Beyond its canonical interphase GEF function, ARHGEF17 serves critical roles in cell cycle regulation and mitotic control. It governs G1/S progression by regulating YAP expression and cyclin B levels 2, and independently acts as an essential spindle assembly checkpoint factor by targeting the kinase Mps1 to kinetochores 3. In cancer, ARHGEF17 is activated by Gβγ signaling downstream of LPA receptors, promoting lung cancer cell migration and metastatic dissemination; elevated expression correlates with reduced survival in advanced-stage patients 4. Disease associations include keratoconus as a cytoskeleton-related candidate gene 5, neurodevelopmental disorders with intellectual disability and microcephaly caused by biallelic ARHGEF17 variants 6, and potential melanoma tumor suppressor inactivation 7. ARHGEF17 is also dysregulated in HIV-associated neuronal pathology 8. Its endothelial expression makes it a potential therapeutic target for vascular inflammation and tumor transendothelial metastasis 1.