Peli3, short for Pellino E3 Ubiquitin Protein Ligase Family Member 3, is an E3 ubiquitin ligase and scaffold protein involved in multiple signaling pathways, such as TLR4-signaling. It plays significant roles in various biological processes including inflammation, cell growth, and survival, and is thus of great biological importance. Genetic models, like knockout mice, have been crucial in studying its functions [4].

In non-small cell lung cancer (NSCLC), Peli3 is aberrantly up-regulated and high levels are associated with poor prognosis. Peli3-deficiency significantly inhibits cell viability, colony formation, migration, and invasion. Also, miR-365a-5p negatively regulates Peli3, and dysregulation of the miR-365a-5p-Peli3 signaling axis is important in NSCLC [1].

In acetaminophen-induced liver injury, whole-body Peli3-/-knockout and adenovirus-mediated Peli3 knockdown mice show reduced liver injury, with decreased mitochondrial and lysosomal damage. Peli3 binds to GSK3β and induces its K63-mediated polyubiquitination, affecting GSK3β phosphorylation and mitochondrial translocation [2].

For infectious osteomyelitis, knocking down Peli3 in RAW264.7 cells increases inflammatory cytokines after LPS stimulation, and Peli3-deficient mice have more severe osteomyelitis symptoms. Peli3 targets and degrades RIPK2 through K48-linked ubiquitination, negatively modulating osteomyelitis [3].

In colitis-associated colorectal cancer (CAC), Peli3-deficient mice in a CAC model show that Peli3 promotes colorectal carcinogenesis by enhancing TLR4-mediated inflammation through ubiquitination-dependent degradation of interferon regulatory factor 4 [5].

In conclusion, Peli3 is a key regulator in multiple biological processes and diseases. Studies using Peli3 KO mouse models have revealed its role in NSCLC, liver injury, osteomyelitis, and CAC, highlighting its potential as a therapeutic target in these disease areas.