FCRL5 is a transmembrane receptor that functions as a dual-role coreceptor in B-cell immune responses. As a negative regulator, FCRL5 inhibits B-cell receptor (BCR) signaling in isolation; however, upon simultaneous engagement with complement receptor 2 (CR2) and BCR, it enhances calcium signaling beyond CR2-BCR costimulation alone 1. FCRL5 expression marks functionally distinct B-cell subsets. FcRL5+T-bet+ effector memory B cells demonstrate superior capacity for rapid differentiation into antibody-secreting cells and correlate with durable humoral immunity following influenza vaccination 2. In regulatory B cells (Bregs), FCRL5 is a marker of organ-specific subsets with immunosuppressive properties 3. FCRL5 expression is dynamically regulated by BCR, TLR9, and cytokine signaling, with expression patterns overlapping with CD11c regulation 4. Clinically, FCRL5 holds significant diagnostic and prognostic value in multiple sclerosis, with elevated cerebrospinal fluid FCRL5 predicting new brain lesions 5. In cancer immunotherapy, FCRL5+ memory B-cell signatures predict immunotherapy response in non-small cell lung cancer 6, while FCRL5-directed CAR-T cells demonstrate potent antitumor activity in multiple myeloma 7. Anti-FcRH5/CD3 bispecific antibodies effectively kill myeloma cells at picomolar concentrations 8.