Peli3, short for Pellino E3 Ubiquitin Protein Ligase Family Member 3, is a RING-type E3 ubiquitin ligase. It is involved in multiple signaling pathways, such as TLR4-signaling, and plays important roles in regulating inflammation, cell growth, and disease-related processes [3,4]. Genetic models, like knockout mice, have been crucial in studying its functions.

Whole-body Peli3 knockout (KO) mice showed reduced centrilobular cell death, immune cell infiltration, and liver injury biomarkers upon acetaminophen treatment, indicating Peli3's role in acetaminophen-induced liver injury [1]. Peli3-deficient mice infected with Staphylococcus aureus had more severe osteomyelitis symptoms, as Peli3 negatively modulates osteomyelitis by degrading RIPK2 [2]. In an azoxymethane/dextran sulphate sodium-induced colitis-associated colorectal cancer (CAC) model, ablation of Peli3 reduced inflammatory signaling activation at the early stage of carcinogenesis, suggesting Peli3 promotes CAC development [4].

In conclusion, Peli3 is essential in regulating inflammation-related biological processes. The use of Peli3 KO mouse models has revealed its significant contributions to diseases like acetaminophen-induced liver injury, infectious osteomyelitis, and colitis-associated colorectal cancer, providing insights into disease mechanisms and potential therapeutic targets.