TRIM45, a member of the TRIM (Tripartite motif) protein family, is a ubiquitin E3 ligase. It contains a RING finger, two B-boxes, a coiled-coil domain, and a filamin-type immunoglobulin domain. TRIM45 is involved in various biological processes such as cell proliferation, differentiation, and development, and is associated with pathways like MAPK and NF-κB [7,8].

Knocking down TRIM45 protected against neuronal damage and cognitive impairment in septic mice, as it inhibited microglial pyroptosis and the secretion of inflammatory cytokines through the Atg5/NLRP3 axis [1]. In cerebral ischemia and reperfusion injury, microglia-specific knockdown of TRIM45 reduced infarct size, mitigated neurological deficit scores, and improved cognitive function by suppressing microglia-mediated neuroinflammation via the TRIM45-TAB2-NF-κB axis [2]. In non-alcoholic steatohepatitis (NASH)-progressed hepatocellular carcinoma (HCC), TRIM45 promoted fatty acid synthesis and accelerated the NASH-to-HCC transition by catalyzing FABP5 ubiquitylation [3]. In non-small cell lung cancer, overexpression of TRIM45 induced G1 arrest and promoted apoptosis [4]. In zebrafish embryos, knockdown of trim45 reduced the size of the diencephalon and eye [5]. In glioma, knockout of TRIM45 promoted cell proliferation and inhibited apoptosis [6]. In chicken cells, knockdown of TRIM45 enhanced ALV-J replication [9].

In conclusion, TRIM45 plays diverse roles in different biological processes and diseases. Gene-knockout and knockdown models in mice, zebrafish, and chicken cells have been crucial in revealing its functions. In diseases such as septic encephalopathy, cerebral ischemia, NASH-progressed HCC, non-small cell lung cancer, glioma, and ALV-J infection, TRIM45 either promotes or suppresses disease-related processes, highlighting its potential as a therapeutic target.