RTKN (rhotekin) is a Rho GTPase effector protein that functions as an oncogenic mediator in multiple cancer types. Structurally, RTKN binds small GTPases and regulates actin cytoskeletal organization and cell contractility 1. Mechanistically, RTKN mediates Rho signaling to activate NF-κB, a transcription factor that promotes cell survival 23. This NF-κB activation confers resistance to apoptosis by inducing expression of antiapoptotic genes including cIAP-2, BCl-xL, and A1 3. Clinically, RTKN is significantly overexpressed in multiple solid tumors including bladder 4, lung 5, gastric 2, and colon cancers 67. In lung adenocarcinoma, RTKN knockdown inhibits cell cycle progression by reducing CDK1/CDK2 and MCM2/MCM6 expression, resulting in S-phase arrest and increased apoptosis 5. In colon cancer, the tumor suppressor microRNA let-7a directly targets RTKN to inhibit growth and metastasis 6. Recently, RTKN was identified as a negative regulator of TRPC6 calcium channels through modulation of channel trafficking 1. In hepatocellular carcinoma, RTKN promotes β-catenin expression via AKT phosphorylation, increasing PD-L1 and impairing anti-tumor immunity 8. These findings suggest RTKN inhibition represents a promising therapeutic strategy across multiple cancer types.