LILRA3 (leukocyte immunoglobulin like receptor A3) encodes a unique soluble member of the LILR family that functions as an immunomodulatory receptor with both activating and inhibitory properties 1. Unlike other LILRA receptors that mediate immune activation, LILRA3 is secreted as a soluble protein and acts as a receptor for HLA class I molecules, though with reduced affinity compared to LILRB1 or LILRB2 1. The gene contains a common 6.7kbp deletion variant that completely abolishes LILRA3 protein production when present homozygously 2. LILRA3 demonstrates significant clinical relevance as a biomarker of disease severity and inflammatory processes. Serum LILRA3 levels are significantly elevated in multiple sclerosis patients, particularly those with primary progressive disease, and serve as a strong independent marker of disease severity 2. The protein is also aberrantly expressed in antiphospholipid syndrome, especially in patients with thrombotic manifestations, and correlates with neutrophil extracellular trap formation 3. Additionally, LILRA3 shows associations with autoimmune diseases including Takayasu arteritis, where it demonstrates epistatic interactions with HLA-B*52 4, and chr19 spontaneous urticaria 5. The receptor can be induced by TLR8 activation in healthy individuals, though this response is impaired in HIV infection 6.