Fc receptor-like protein 4 (FCRL4)

Fc receptor-like protein 4 (FCRL4) is a transmembrane immunoregulatory receptor belonging to the immunoglobulin superfamily, predominantly expressed on a subset of tissue-resident, mucosal, and synovial memory B cells[2][4][5]. Structurally, FCRL4 has an extracellular domain homologous to classical Fc receptors and binds immunoglobulin A (IgA)[1][2]. The cytoplasmic tail contains immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that recruit phosphatases (e.g., SHP-1, SHP-2) to potently inhibit BCR signaling, block early activation events, and dampen immune synapse formation[2][6]. FCRL4^+ B cells present an “exhausted” phenotype and are implicated in chronic infection and autoimmune inflammation, especially in rheumatoid arthritis, where these cells produce cytokines such as RANKL and can contribute to local tissue damage[2][4]. FCRL4 represents a potential therapeutic and diagnostic target, particularly for modulating pathogenic B cell responses in chronic autoimmune and inflammatory disorders[1][4].

Other names

Fc receptor-like 4FCRH4IFGP2IRTA1CD307dfcR-like protein 4fc receptor homolog 4hIFGP2immune receptor translocation-associated protein 1IGFP2IFGP family protein 2gp42immunoglobulin superfamily Fc receptorimmunoglobulin superfamily receptor translocation associated 1

Antagonistic (blocking) antibodies inhibit IgA binding and receptor function[1]. Potential down-modulation of pathogenic B cell activity and inhibition of immune complex–mediated activation[1].