LILRA4 is a leukocyte immunoglobulin-like receptor that functions as a coreceptor to negatively regulate innate immune responses, primarily in plasmacytoid dendritic cells (pDCs). 12 It signals through association with FCER1G to activate Src family and Syk kinases, triggering intracellular calcium mobilization. 12 LILRA4 acts as a negative regulator of TLR7 and TLR9 signaling cascades, downregulating type I interferon (IFNA1, IFNA2, IFNA4, IFNB1) and TNF production in response to viral infections and CpG dinucleotides. 123 It also suppresses interferon production when HIV-1-infected cells express BST2. 4 Notably, LILRA4 preserves pDC differentiation into antigen-presenting cells despite its inhibitory function. 3 Clinically, genetic variants in LILRA4 show protective associations with autoimmune conditions: a variant near LILRA4/LILRA5 was suggestively associated with reduced autoimmune hepatitis risk (rs11084330, OR=0.65), 5 and LILRA4 was identified as a core gene for rheumatoid arthritis through genome-wide trans effects analysis, supported by Mendelian randomization. 6 These findings highlight LILRA4's role as an immune checkpoint regulator with therapeutic potential in autoimmune diseases.