Trim33, also known as TIF-1γ, is a transcriptional repressor and E3 ubiquitin ligase. It is involved in multiple biological processes, including regulating signaling pathways like TGF-β/SMAD, and is crucial for maintaining genome stability. It plays roles in cell differentiation, development, and homeostasis, and its dysregulation is associated with various diseases [1,5,7]. Genetic mouse models, such as gene knockout (KO) and conditional knockout (CKO), have been instrumental in studying Trim33's functions.

In KO mouse models, Trim33 has been shown to have diverse roles. Hematopoietic-specific Trim33 knockout sensitized mice to bleomycin-induced pulmonary fibrosis, indicating its role as a negative regulator of lung fibrosis [1]. In dendritic cell (DC) development, conditional deletion of Trim33 in vivo caused rapid loss of DC progenitors, pDCs, and cDC1 subset, revealing its essential role in DC differentiation [2,6]. In prostate cancer, TRIM33 knockdown sensitized PCa cells to AR antagonists, suggesting its role as an oncogenic AR coactivator [3]. In esophageal squamous cell carcinoma, TRIM33 promotes tumor growth by regulating P53-related glycolysis [4]. Loss of Trim33 in multiple myeloma is associated with genomic instability and increased sensitivity to PARP inhibitors [7]. In hepatocellular carcinoma, TRIM33 promotes susceptibility to ferroptosis through ubiquitination of TFRC [8]. Epiblast-specific Trim33 mutant embryos had cardiac defects, highlighting its role in pre-cardiogenic mesoderm development [9].

In conclusion, Trim33 is a multifunctional protein involved in cell differentiation, disease development, and maintaining genome integrity. The KO/CKO mouse models have significantly contributed to understanding its roles in diseases like pulmonary fibrosis, cancer, and multiple myeloma, providing potential therapeutic targets for these conditions.