RTKN2 (rhotekin 2) is a Rho-GTPase effector protein with dual roles in immune regulation and cancer progression. In immune homeostasis, RTKN2 is directly transactivated by transcription factor Pbx1 and plays a critical role in maintaining regulatory T (Treg) cell homeostasis and stability, preventing autoimmune disease such as lupus 1. RTKN2 regulates cell survival through NF-κB signaling and BCL-2 gene expression in CD4+ T cells, functioning as a key survival signal 2. In cancer contexts, RTKN2 demonstrates paradoxical tissue-dependent functions. In bladder cancer, RTKN2 is overexpressed and promotes proliferation through cell cycle progression via CDK2 and MCM proteins; RTKN2 knockdown induces G1 arrest and apoptosis 3. Similarly, in colorectal cancer, circZFR-mediated RTKN2 upregulation promotes tumor growth and metastasis 4, and in gastric cancer, RTKN2 enhances radioresistance via Wnt/β-catenin activation 5. However, in lung adenocarcinoma and non-small-cell lung cancer, RTKN2 expression is reduced, and RTKN2 overexpression suppresses proliferation, migration, and glycolysis through NF-κB pathway inhibition, suggesting a tumor-suppressive role 678. These findings indicate RTKN2 functions contextually as both an immune regulator and cancer-associated protein with therapeutic potential across multiple malignancies.