Sialic acid-binding Ig-like lectin 5 (Siglec-5)

Human Siglec-5 (CD170) is an inhibitory receptor belonging to the CD33-related Siglec family, primarily expressed on myeloid cells such as neutrophils, monocytes, and macrophages, as well as activated T cells [1, 4, 9]. It functions as a glyco-immune checkpoint by binding to sialylated glycans or specific bacterial proteins (e.g., Group B Streptococcus β-protein) and recruiting tyrosine phosphatases SHP-1 and SHP-2 via its cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) to suppress immune activation [1, 8, 11, 12]. Siglec-5 is implicated in tumor immune evasion, chronic infections, and inflammatory conditions such as sepsis and Sjögren's syndrome [9, 12, 14, 17]. Therapeutic strategies focus on blocking Siglec-5 to enhance anti-tumor immunity or using its soluble form as a diagnostic biomarker for cardiovascular and autoimmune diseases [9, 11, 16, 17]. A significant challenge in targeting Siglec-5 is its high sequence homology with the activating receptor Siglec-14, which requires highly specific agents to avoid unintended inflammatory or suppressive effects [2, 10, 11].

Other names

CD170OB-BP2CD33L2OBBP2Sialic acid-binding immunoglobulin-like lectin 5

Antagonism of inhibitory signaling to enhance anti-tumor or anti-microbial immune responses; recruitment of SHP-1 and SHP-2 phosphatases via ITIM motifs to inhibit cellular activation [1, 8, 9, 11].