Ltn1, also known as listerin, is a key component of the ribosome-associated protein quality control (RQC) pathway. It functions as an E3 ubiquitin ligase, targeting aberrant nascent polypeptides for proteasomal degradation. RQC is crucial for eliminating truncated polypeptides produced during interrupted translation, which could otherwise have deleterious effects on cells [2,3,5].

Ltn1 deficiency enhances the innate antiviral response to RNA virus infection, as it promotes the degradation of RIG-I and IFIH1/MDA5 through the ESCRT-dependent pathway, negatively regulating RLR-mediated antiviral innate immunity [1]. In hepatocellular carcinoma, in vivo CRISPR KO screens identified LTN1 as a novel tumor suppressor. Forced expression of LTN1 decreased cell growth, while knockdown increased it, by ubiquitinating and destabilizing the IGF2BP1 protein [4]. Listerin (Ltn1) also promotes cGAS protein degradation through the ESCRT pathway, negatively regulating cGAS-mediated immune response. Listerin deficiency enhances the innate antiviral response to herpes simplex virus 1 infection, and its genetic deletion deteriorates neuroinflammation and ALS disease progress in an ALS mice model [6].

In conclusion, Ltn1 plays essential roles in protein quality control, antiviral immune response, and cancer development. Gene knockout models, such as in the study of RNA virus response, hepatocellular carcinoma, and ALS, have revealed its significance in these biological processes and disease conditions, providing potential targets for intervention in viral infection and cancer treatment, as well as new insights into neurodegenerative disease mechanisms.