Bcl10, or B-cell lymphoma/leukemia 10, is a key protein. It forms the CARMA-BCL10-MALT1 (CBM) complex, regulating apoptosis via activating NF-κB signaling. It also participates in innate and adaptive immune signaling downstream of CARMA/caspase-recruitment domain (CARD) scaffold proteins [1,3].

In DNA damage response, cytoplasmic Bcl10 enters the nucleus to promote DNA damage repair, such as histone ubiquitination and recruitment of homologous recombination (HR) repair factors, contributing to cell survival [1]. In immune-related aspects, human Bcl10 deficiency causes combined immunodeficiency [2]. In activated B cell-like diffuse large B-cell lymphomas (ABC-DLBCL), Bcl10 mutations, including missense mutations of the CARD domain and truncation of its C-terminal tail, lead to distinct dependencies. These mutants are less dependent on upstream CARD11 activation and show resistance to BTK inhibitors, with truncating mutants being hypersensitive to MALT1 inhibitors [4]. Also, Bcl10 is involved in type I interferon (IFN) expression in response to DNA virus infection, where DNA virus infection triggers its recruitment to the STING-TBK1 complex, phosphorylation by TBK1, droplet-like condensation, and subsequent innate immune response induction [5].

In conclusion, Bcl10 is crucial in apoptosis regulation, immune signaling, DNA damage repair, and response to DNA virus infection. Studies on Bcl10, including those using genetic models like gene knockout mouse models, contribute to understanding its role in diseases such as immunodeficiency and ABC-DLBCL, providing potential directions for precision therapy [1,2,4].