RWDD4 (RWD domain containing 4) is a protein-binding protein implicated in cancer progression and metastasis. In prostate cancer, RWDD4 functions as a germline modifier of metastatic potential; genome-wide mapping in a mouse model identified RWDD4 as a functional effector of a metastasis modifier locus, and ectopic overexpression of RWDD4 increased aggressiveness of human prostate cancer cell lines 1. Analysis of over 5,300 prostate cancer patient samples revealed correlations between RWDD4 genetic variants, expression levels, cancer aggressiveness, and patient survival 1. In bladder cancer, RWDD4 serves as a direct target of the tumor-suppressive microRNA miR-506; RWDD4 downregulation suppresses bladder cancer cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition 2. In breast ductal carcinoma in situ, RWDD4 was identified as a high-frequency, high-risk mutant gene with downregulated expression compared to normal tissues 3. Collectively, these findings suggest RWDD4 promotes cancer progression across multiple malignancies and may represent a therapeutic target.