Fcrl5, also known as FcRH5/IRTA2/CD307, is a surface protein selectively expressed on B cells and plasma cells. It plays a role in B-cell function regulation, with its expression being associated with pathways related to B-cell activation, anergy, and differentiation. It has significance in the context of immune-related biological processes and diseases [2,3].

In multiple myeloma, Fcrl5 is upregulated, making it a promising target for therapies. Fcrl5-directed CAR-T cells incorporating interleukin-15 showed potent antitumor efficacy in vitro and in xenograft models, effectively inhibiting MM cell proliferation [1]. Also, Fcrl5 ADCs were efficacious in vitro and in vivo, especially in combination with drugs like bortezomib or lenalidomide [4].

In autoimmune diseases, B cell-specific Fcrl5 transgenic mice (a form of over-expression model, related to functional studies) showed that Fcrl5 overexpression in B cells caused systemic autoimmunity with age, and its upregulation in B cells exacerbated a systemic lupus erythematosus-like disease model. It also broke B cell anergy and facilitated toll-like receptor signaling [2].

In conclusion, Fcrl5 is crucial in B-cell-mediated immunity. Model-based research, such as transgenic mouse models in autoimmune diseases and in vivo models in multiple myeloma, has revealed its role in disease pathogenesis. In multiple myeloma, it shows potential as a therapeutic target, and in autoimmune diseases, it is involved in disrupting B cell anergy and contributing to disease development.