ARHGAP4 is a Rho GTPase-activating protein that negatively regulates Rho family GTPases and inhibits stress fiber organization 1. Mechanistically, ARHGAP4 forms a complex with septin proteins (SEPT2/SEPT9) via its Rho-GAP and SH3 domains to modulate integrin-mediated focal adhesions and cytoskeletal reorganization 2. The protein also functions by binding p53 to inhibit DRAM1 signaling 1. ARHGAP4 has emerged as a critical oncogenic driver across multiple cancer types. In acute myeloid leukemia, ARHGAP4 overexpression promotes leukemogenesis and predicts poor prognosis, with knockdown inducing apoptosis and impairing tumor progression 1. In colon cancer, elevated ARHGAP4 promotes metastasis through TGF-β/Smad signaling and correlates with T cell exhaustion markers and reduced overall survival 34. Similarly, ARHGAP4 overexpression in gastric scirrhous-type cancer independently predicts poor prognosis and recurrence 5. Additionally, ARHGAP4 was identified as a co-diagnostic biomarker in both Alzheimer's disease and metabolic syndrome 6, while ARHGAP4 deletions cause intellectual disability and nephrogenic diabetes insipidus in males 7. Clinically, ARHGAP4 represents a promising therapeutic target and prognostic biomarker for cancer stratification and treatment selection.