TRIM21, also known as Ro52, is a RING finger domain-containing E3 ubiquitin ligase. It plays crucial roles in multiple immunological processes, such as antibody-dependent intracellular neutralization, antiviral response, and protein ubiquitination. It is also involved in various signaling pathways related to cell survival, proliferation, and apoptosis, and is of great biological importance in maintaining normal physiological functions and in disease-related processes [3].

In cancer, TRIM21's role is complex. In nasopharyngeal carcinoma, knockout of TRIM21 potentiates the antigen-presenting capacity of NPC cells, activates cytotoxic T cell-mediated antitumour immunity, and modulates the cGAS/STING cytosolic DNA sensing pathway. High TRIM21 expression in NPC patients is associated with poor prognosis and early tumour relapse after radiotherapy [1]. In some human cancers like colorectal and breast cancers, low TRIM21 expression is associated with poor prognosis in patients with mutant p53, as TRIM21 deficiency promotes mutant p53 accumulation and its gain-of-function in tumorigenesis [4].

In obesity-induced inflammation, targeting macrophage TRIM21 with antisense oligonucleotide-loaded red blood cell extracellular vesicles effectively inhibits obesity-induced inflammation and related metabolic disorders. UBE2M-mediated neddylation of TRIM21 is crucial for obesity-related inflammation in macrophages [2].

In acute kidney injury, loss of TRIM21 alleviates ferroptosis induced by ischemia/reperfusion, as TRIM21 ubiquitylates GPX4 and promotes ferroptosis [5].

In conclusion, TRIM21 is a key E3 ubiquitin ligase involved in diverse biological processes. Studies using gene knockout models in mice have revealed its significance in cancer, obesity-related inflammation, and acute kidney injury. These findings provide potential targets for treating these diseases, highlighting the importance of TRIM21 in understanding disease mechanisms and developing therapeutic strategies.