Trim27, a RING-mediated E3 ubiquitin ligase and a member of the TRIM protein family, can mark other proteins like PTEN, IκBα and p53 for degradation, regulating multiple signaling pathways related to cell proliferation, differentiation, and apoptosis [3]. It is involved in pathways such as Wnt/β -catenin, autophagy-related pathways, and endosomal trafficking regulation.

Knockout of Trim27 in mice causes IBS-like symptoms, including increased visceral hyperalgesia and abnormal stool features, revealing its role in maintaining gut homeostasis through promoting intestinal stem cell self-renewal via stabilizing β -catenin and activating Wnt/β -catenin signaling [1]. In tuberculosis, Trim27 enhances host autophagy flux in an E3 ligase activity-independent manner to elicit protective immunity against Mycobacterium tuberculosis [2]. In cancer-related studies, Trim27 knockout in mouse models shows differential regulation of tumorigenesis and metastasis. It cooperates with STK38L to inhibit ULK1-mediated autophagy and promote tumorigenesis [4].

In conclusion, Trim27 plays crucial roles in maintaining gut homeostasis, anti-tuberculosis immunity, and the regulation of autophagy and tumorigenesis. Gene knockout mouse models have been instrumental in revealing these functions, providing potential therapeutic targets for diseases such as IBS, tuberculosis, and cancer.