ARHGAP8 (Rho GTPase activating protein 8) is a scaffold GAP protein that regulates Rho family GTPases by catalyzing GTP hydrolysis to convert them to inactive GDP-bound states 1. The protein contains distinctive functional domains including a C-terminal RHOGAP domain, central SH3-binding motif, and N-terminal BCH/Sec14p-like domain 2. Beyond canonical RhoA inactivation, ARHGAP8 functions as a dual-function scaffold that recruits the RacGEF Vav1 to activate Rac1, synchronizing Rac and Rho signaling for polarized cell motility, invadopodium formation, and cancer cell migration 3. In schizophrenia pathogenesis, dysregulated ARHGAP8 via the THUMPD3-AS1/miR-485-5p axis activates ROCK2 through RhoB/C-mediated compensatory mechanisms, disrupting actin cytoskeletal remodeling and generating immature dendritic spines and synaptic ultrastructural defects 4. ARHGAP8 is highly expressed in colorectal and rectal cancer tissues 25, with elevated expression correlating with tumor stage and lymph node metastasis 5. Clinically, low ARHGAP8 expression predicts improved sensitivity to neoadjuvant chemotherapy in locally advanced rectal cancer 5. ARHGAP8 variants and dysregulation are implicated in psychiatric disorders, including association with binge eating behavior in bipolar disorder 6. ARHGAP8 is also a component of a four-gene biomarker panel (with GFUS, NBL1, and ACTB) showing high diagnostic and prognostic utility in prostate cancer 7.