SIGLEC5 (sialic acid binding Ig-like lectin 5) functions as a cell surface adhesion molecule that mediates sialic acid-dependent binding interactions 1. The protein serves as a glycoimmune checkpoint receptor that can inhibit immune cell activation through recognition of sialylated glycans 2. In monocytes and macrophages, SIGLEC5 acts as an inhibitory receptor that binds to glycoRNAs on cell surfaces, facilitating monocyte adhesion to endothelial cells 1. The protein's expression is regulated by hypoxia-inducible factor 1α (HIF1α) and becomes elevated during inflammatory conditions 3. SIGLEC5 interacts with P-selectin glycoprotein ligand-1 (PSGL1) to suppress CD8+ T-cell proliferation, contributing to immune exhaustion in sepsis 3. The gene contains regulatory variants that affect transcription factor binding, with alleles influencing ERG and MAFB binding sites that modulate SIGLEC5 expression levels 4. These regulatory polymorphisms have been associated with periodontitis susceptibility and interact with other genetic loci affecting wound healing pathways 5. In cancer contexts, SIGLEC5-expressing tumor macrophages are associated with immunotherapy resistance, while therapeutic desialylation can block SIGLEC5-mediated immune suppression to enhance cellular immunotherapy efficacy 26.