FCRL3 is an Fc receptor-like protein with dual regulatory roles in adaptive and innate immunity. In B cells, FCRL3 promotes TLR9-induced proliferation and activation while inhibiting antibody production and plasma cell differentiation through enhancement of NF-κB and MAPK signaling 1. Conversely, FCRL3 exerts inhibitory effects on BCR-mediated signaling by suppressing tyrosine phosphorylation, calcium mobilization, and activation-induced cell death 2. In regulatory T cells, FCRL3 expression is associated with a memory phenotype and reduced suppressive capacity 34. FCRL3 also functions in gamete recognition, acting as an IZUMO1 receptor on oocytes during sperm-egg fusion 5. Genetically determined FCRL3 levels show protective effects against multiple sclerosis, with increased circulating FCRL3 associated with reduced MS risk (OR=0.83) 67. FCRL3 polymorphisms, particularly the -169T/C variant, increase rheumatoid arthritis susceptibility 8. FCRL3 is also identified as a risk locus for primary biliary cholangitis 9 and thyroid autoimmunity 10. In kidney allograft rejection, FCRL3-expressing NK cells suggest antibody-dependent cytotoxicity as a rejection mechanism 11. Dysregulated FCRL3 expression in lupus-associated regulatory T cells may contribute to impaired immune regulation in systemic lupus erythematosus 12.