Fc receptor-like protein 5 (FCRL5) (FCRL5)

Fc receptor-like protein 5 (FCRL5), also known as FcRH5 or CD307, is a type I transmembrane glycoprotein belonging to the immunoglobulin superfamily [2, 5]. It is expressed exclusively within the B-cell lineage, with levels increasing during maturation and reaching peak expression on plasma cells [1, 6]. In the context of hematologic malignancies, FCRL5 is significantly overexpressed on malignant plasma cells in multiple myeloma, especially in cases involving 1q21 chromosomal gains [2, 10]. Biologically, it serves as a receptor for intact IgG and functions as a dual-role coreceptor that can either enhance or inhibit B-cell receptor signaling via its cytoplasmic ITAM and ITIM motifs [5, 12, 16]. Due to its restricted expression and high prevalence in myeloma, FCRL5 has become a prominent therapeutic target for novel immunotherapies [3, 8]. Current clinical developments include bispecific T-cell engagers like cevostamab, which redirect T cells to kill FCRL5-positive tumor cells, as well as antibody-drug conjugates and CAR-T cell therapies [2, 6, 10]. These treatments aim to provide effective options for patients with relapsed or refractory disease, including those who have failed BCMA-targeted therapies [6, 10].

Other names

Fc receptor homolog 5FcRH5IRTA2Immune receptor translocation-associated protein 2CD307eBXMAS1Fc receptor-like protein 5

T-cell redirection via bispecific antibody binding, targeted delivery of cytotoxic agents via antibody-drug conjugates, and direct cellular cytotoxicity via CAR-T cells [2, 3, 6].