TRIM15, a member of the tripartite motif (TRIM) protein family, functions as an E3 ubiquitin ligase. It is involved in multiple cellular processes, including signal transduction, apoptosis, and autophagy, and plays a significant role in various biological pathways such as the ERK, AKT/FOXO1, and Keap1-Nrf2 signaling pathways. Its abnormal regulation is associated with numerous diseases, especially cancers, highlighting its importance in understanding disease mechanisms [1,2,3].

In melanoma, down-regulation of TRIM15 inhibits the growth of both drug-responsive and drug-resistant melanomas, suggesting its role in cancer cell growth regulation [1]. In hepatocellular carcinoma (HCC), TRIM15 is upregulated after tyrosine kinase inhibitor (TKI) treatment and contributes to TKI resistance. Knockdown of TRIM15 may potentially overcome this resistance [2]. In non-small cell lung cancer (NSCLC), TRIM15 knockdown leads to decreased cancer cell proliferation and metastasis [3]. In pancreatic cancer, silencing TRIM15 suppresses cell invasion and migration [5]. In hepatic stellate cells, knockdown of TRIM15 inhibits their activation, indicating its role in liver fibrosis [6]. In chondrocytes, conditional deletion of Trim15 in mouse chondrocytes impairs skeletal growth and affects OA progression [4].

In conclusion, TRIM15 is a crucial E3 ubiquitin ligase involved in multiple biological processes and disease conditions. Gene knockout or conditional knockout mouse models, along with other loss-of-function experiments, have significantly contributed to understanding its role in cancer development, drug resistance, liver fibrosis, and osteoarthritis, providing potential therapeutic targets for these diseases.