FCRL5

Fc receptor-like 5 (FCRL5), also known as immunoglobulin receptor translocation-associated protein 2 (IRTA2) or CD307e, is a transmembrane glycoprotein predominantly expressed on mature B cells. Unlike classical Fc receptors, FCRL5 lacks conserved Fc-binding motifs but contains both immunoreceptor tyrosine-based activation (ITAM) and inhibitory (ITIM) domains, enabling dual modulation of B-cell receptor (BCR) signaling. It regulates B-cell activation, differentiation, and antibody production through interactions with SYK and PI3K/AKT pathways. Dysregulated FCRL5 expression is implicated in autoimmune diseases (e.g., systemic lupus erythematosus and rheumatoid arthritis) and B-cell malignancies, particularly chronic lymphocytic leukemia and multiple myeloma. Recent studies highlight its potential as a therapeutic target, with anti-FCRL5 monoclonal antibodies (e.g., UC-961) demonstrating preclinical efficacy in depleting malignant B cells. Clinical trials exploring FCRL5-targeted CAR-T therapies and antibody-drug conjugates are emerging, though none have reached late-stage development as of 2023. Its unique extracellular immunoglobulin-like domains make it a distinctive biomarker for pathogenic B-cell subsets.