Tmem176b, a member of the membrane spanning 4-domains (MS4) family, is an intracellular cation channel. It serves as a dual immunoregulator, being involved in modulating immune responses. It can both inhibit effector immune responses in certain settings and promote immunity by supporting antigen presentation. It also potentially regulates type 2 and 3 immunity, and is associated with pathways like inflammasome activation, DC biology modulation, and CD8+ T cell responses [1].

Disruption of Tmem176b in mice contributes to CD8+ T cell-mediated tumor growth inhibition by unleashing inflammasome activation, enhancing the antitumor activity of anti-CTLA-4 antibodies through caspase-1/IL-1β activation [2]. In triple-negative breast cancer, silencing Tmem176B in cell lines impaired cell proliferation, and in vivo studies showed attenuated tumor growth. The AKT/mTOR signaling pathway was repressed in Tmem176B-silenced cells [3]. In lung adenocarcinoma, Tmem176B promoted cellular functions like proliferation, invasion, and regulated EMT via the FGFR1/JNK/Vimentin/Snail signaling cascade [4]. In ovarian cancer, Tmem176B inhibited cancer progression by regulating EMT via the Wnt/β-catenin signaling pathway, with lower expression correlating with a worse prognosis [5].

In summary, Tmem176b plays a crucial role in immune regulation and is involved in multiple disease-related processes. Gene knockout or knockdown studies in mouse models and cell lines have revealed its significance in tumor immunity and cancer progression, providing potential therapeutic targets for cancer treatment. Its role in regulating key signaling pathways in different cancers and its dual function in immune responses highlight its importance in biomedical research [1-4, 7].