FCRL6 is a transmembrane glycoprotein immunoreceptor predominantly expressed on mature cytotoxic lymphocytes, including CD8+ T cells, NK cells, and gamma-delta T cells 1. It functions as an MHC class II receptor 2 and recruits inhibitory phosphatases (SHP-1, SHP-2, SHIP-1, SHIP-2) and adaptor proteins through phosphorylated cytoplasmic tyrosines, conferring inhibitory signaling properties 3. Unlike other Fc receptors, FCRL6 does not bind immunoglobulins 1 and does not independently regulate cytokine production or cytotoxic granule release by NK or CD8+ T cells 41. FCRL6 serves as a biomarker of antigen-experienced, mature cytotoxic lymphocytes 3 and is dysregulated in multiple disease contexts. Its upregulation in HLA-DR+ tumor samples from melanoma, breast, and lung cancer patients who failed PD-1 blockade suggests a mechanistic role in adaptive immune evasion 5. FCRL6 is also significantly altered in systemic lupus erythematosus with renal disease 6, chr1 neuropathic pain 7, and CMV infection in HIV+ individuals, where high FCRL6 expression serves as a biomarker of immune activation 8. These findings position FCRL6 as a potential prognostic marker and therapeutic target across multiple pathologies.