TRIM5, a member of the tripartite motif protein family, is a restriction factor that defends mammalian cells against invading retroviruses like HIV-1 [1,2,4,7]. It recognizes and inactivates the capsid shell of incoming retroviral cores, coordinating the core uncoating and reverse transcription processes of the viral genome [1]. As an E3 ubiquitin ligase, TRIM5 also activates the TAK1 kinase, NF-κB and AP-1 signaling, and transcription of inflammatory cytokines and chemokines [2].

Cells lacking TRIM5 are unable to carry out PRKN-dependent and PRKN-independent mitophagy pathways, showing reduced mitochondrial function and uncontrolled immune activation in response to mitochondrial damage, indicating its role in mitophagy [5]. In hepatocellular carcinoma (HCC), mRNA and protein levels of TRIM5 are significantly upregulated, showing promising clinical prognostic value and strong association with immune cell infiltration [3]. TRIM5 also inhibits Senecavirus A replication by promoting the RIG-I-mediated type I interferon antiviral response [6].

In conclusion, TRIM5 plays essential roles in antiviral defense, mitophagy, and is associated with diseases such as HCC and viral infections. The study of TRIM5 knockout models has provided insights into its role in these biological processes and disease conditions, helping to understand the underlying mechanisms and potentially develop new therapeutic strategies.