TRIM33 is a tumor suppressor in breast cancer, non-small-cell lung cancer, and clear cell renal cell carcinoma and, through its role in β-catenin degradation, prevents brain tumor development and human glioblastoma. TRIM33 also has a role in regulation of the transforming growth factor beta (TGF-β) superfamily. In contrast, TRIM33 can also function as a tumor promotor by preventing apoptosis in B lymphoblastic leukemia, demonstrating that TRIM33 has a range of biological functions. TRIM33 also plays a role in the poly(ADP-ribose) polymerase (PARP)dependent DNA damage response pathway. 23 TRIM66 has also recently been shown to act in the DNA damage response, and binds to H3R2K4 and H3K56Ac. Prior to their identification, biological studies did not distinguish between the two TRIM33 isoforms, TRIM33α and TRIM33β.