ARHGAP40 is a Rho GTPase-activating protein (RhoGAP) that functions as a GTPase activator, converting Rho-type GTPases to their inactive GDP-bound state and thereby regulating actin filament polymerization and small GTPase-mediated signaling in the cytoplasm 1. In normal tissues, ARHGAP40 is robustly expressed in basal cells and benign skin lesions 1, as well as in normal fallopian tubes and benign ovarian tumors 2. However, ARHGAP40 expression is frequently lost in multiple cancer types through an epigenetic mechanism involving CpG island hypermethylation of its promoter region 12. ARHGAP40 downregulation occurs in 93.8% of high-grade serous ovarian carcinomas 2, breast tumors from ATM pathogenic variant carriers 3, and basal cell carcinomas 1, with promoter methylation showing strong inverse correlation with protein expression 2. Clinically, methylated ARHGAP40 circulating tumor DNA was detected in 80% of high-grade serous ovarian cancer patients' plasma but absent in controls, suggesting potential utility as a noninvasive biomarker for early cancer diagnosis and monitoring 2. ARHGAP40 may also serve as a biomarker to distinguish basal cell carcinoma from benign skin lesions 1.