Fcrl5, also known as FcRH5/IRTA2/CD307, is a surface protein selectively expressed on B cells and plasma cells. It plays a role in regulating B-cell function, and its expression can be influenced by different activation signals such as BCR and TLR9 activation [3].

In autoimmune diseases, Fcrl5 upregulation in B cells disrupts B cell anergy, contributing to the pathogenesis of autoimmune diseases. B cell-specific Fcrl5 transgenic mice showed systemic autoimmunity with age, and Fcrl5 upregulation exacerbated the systemic lupus erythematosus-like disease model. This indicates that Fcrl5 is a potential regulator of B cell-mediated autoimmunity [2].

In multiple myeloma, Fcrl5 is considerably upregulated. Fcrl5-directed CAR-T cells incorporating IL-15 exhibit potent antitumor efficacy, effectively inhibiting MM cell proliferation and leading to tumor suppression. Also, Fcrl5 can be a target for antibody-drug conjugates (ADCs) in multiple myeloma treatment, as Fcrl5 ADCs were efficacious in vitro and in vivo [1,4].

In conclusion, Fcrl5 is a key regulator in B-cell-related functions. Studies using transgenic mouse models have revealed its significant role in autoimmune diseases and multiple myeloma, providing potential therapeutic targets for these diseases.