RHPN2 (rhophilin Rho GTPase binding protein 2) is a GTP-Rho binding protein that plays crucial roles in cancer progression and cellular signaling pathways. The protein functions primarily through RhoA/ROCK pathway activation, promoting malignant transformation across multiple cancer types 1. RHPN2 facilitates mesenchymal transformation in glioblastoma by triggering RhoA activation, with gene amplification on chromosome 19 correlating with dramatically decreased patient survival 1. In lung adenocarcinoma, RHPN2 promotes epithelial-mesenchymal transition, cell proliferation, and metastasis, with transcriptional regulation by KLF5 2. The protein also contributes to gefitinib resistance through RhoA/ROCK pathway activation 3. Additionally, RHPN2 promotes proliferation and migration while inhibiting apoptosis in osteosarcoma cells, with high expression correlating with poor prognosis 4. In pancreatic cancer, RHPN2 facilitates proliferation, metastasis, and angiogenesis through circular RNA-mediated regulation 5. Germline variants affecting RHPN2 expression are associated with inherited cancer risk, potentially upregulating cancer-linked pathways through stimulus-responsive RhoA activation 6. These findings establish RHPN2 as a significant oncogene and potential therapeutic target across multiple malignancies.