TRIM16, also known as tripartite motif containing 16, is an E3 ubiquitin ligase. It plays crucial roles in various biological processes such as cell survival, immune response, and oxidative stress regulation [2]. It is associated with multiple pathways including those related to autophagy, antioxidant response, and MAPK signaling [1,3,5]. Its overall biological importance lies in maintaining cellular homeostasis and influencing disease-related processes. Genetic models, especially knockout (KO) and conditional knockout (CKO) mouse models, have been instrumental in studying TRIM16.

In cardiac hypertrophy, Trim16-deficient mice showed exacerbated cardiomyocyte enlargement in vitro and in a transverse aortic constriction-induced cardiac hypertrophy mouse model, while Trim16 overexpression attenuated cardiac hypertrophy. Prdx1 was identified as an essential target of Trim16, with Trim16 interacting with Prdx1 to inhibit its phosphorylation and enhance the downstream Nrf2 pathway [2]. In doxorubicin-induced cardiotoxicity, TRIM16 overexpression in mouse hearts using AAV9-TRIM16 ameliorated cardiac function, suppressed inflammation, ROS generation, apoptosis, and fibrosis. Knockdown of TRIM16 in neonatal rat cardiomyocytes exacerbated these alterations. Mechanistically, OE-TRIM16 augmented the ubiquitination and degradation of p-TAK1, arresting JNK and p38MAPK activation, and also modulated the YAP/Nrf2 pathway [4].

In conclusion, TRIM16 plays essential roles in maintaining cellular function through its involvement in multiple biological processes. Studies using KO/CKO mouse models have revealed its significance in diseases such as pathological cardiac hypertrophy and doxorubicin-induced cardiotoxicity. Understanding TRIM16 can provide potential therapeutic strategies for these and other related diseases.