BRDs are well characterized protein modules comprising approximately 110 amino acids that bind to KAc residues on histones, and many other proteins. Their well-defined tertiary structure comprises a left-handed, antiparallel, four-helical bundle (αA, αB, αC, and αZ), which is structurally-conserved across the family, despite relatively low sequence identity. The KAc binding pocket of most BRDs is hydrophobic but contains structural water molecules at the base of the pocket and, in some cases, in the ZA channel. The ability of these water molecules to be displaced varies between classes of BRDs, and has been exploited to develop selective ligands for certain proteins. The canonical BRDs possess a highly conserved asparagine residue, which forms a hydrogen bond to KAc. However, thirteen non-canonical BRDs exist, twelve of which possess threonine or tyrosine residues at this position that are, in principle, capable of hydrogenbonding to KAc. One of these is TRIM28, in which the asparagine residue is replaced by a threonine. In addition, the 17-amino acid insertion in TRIM33α (vide infra) moves this asparagine out of the KAc-binding pocket, resulting in no obvious residue that can interact with KAc at this position. The inherent affinity of BRDs for a single KAc amino acid is low, and further affinity is derived from interactions with the cognate peptide/protein, which also confer selectivity for given acetylated binding partners. These PHD and BRD modules enable chromatin binding of proteins, and consistent with this, deletion of either the BRD or the PHD in TRIM33 prevents its localization to sites of DNA breaks. The biological functions of TRIM24, TRIM28, TRIM33 and TRIM66 have been investigated, and some key findings are briefly described below. Overexpression of TRIM24 is connected to tumor progression and poor prognosis in breast cancer, and significant upregulation has been observed in cancers including gastric cancer, non-small-cell lung cancer, 26 leukemia, prostate cancer, and hepatocellular carcinoma. Knockdown of TRIM24 in colon cancer cell lines suppressed tumor growth and induces apoptosis. Despite mouse models indicating that TRIM24 can act as a liver-specific tumor suppressor, most studies show that TRIM24 is an oncogene when overexpressed.