SIGLEC14 is a member of the sialic acid-binding immunoglobulin-like lectin (Siglec) family, primarily expressed on immune cells such as macrophages and neutrophils. Unlike many inhibitory Siglecs that contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs), SIGLEC14 associates with activating adaptor proteins (e.g., DAP12) to trigger pro-inflammatory responses upon ligand binding. It recognizes sialylated glycans on pathogens or host cells, playing a role in pathogen sensing and immune regulation. Interestingly, the SIGLEC14 gene exhibits a genomic deletion polymorphism in humans, resulting in its pseudogenization (SIGLEC14P) in certain populations. This deletion is linked to evolutionary adaptation, potentially influencing susceptibility to infections or inflammatory diseases. Antibodies targeting SIGLEC14 are valuable tools for studying its function, expression patterns, and involvement in diseases like chronic obstructive pulmonary disease (COPD), cancer, or neurodegenerative disorders. Recent research explores its dual role in promoting inflammation and modulating immune tolerance, highlighting its therapeutic potential. However, challenges remain in understanding its ligand specificity and signaling crosstalk with inhibitory Siglecs (e.g., SIGLEC5), which may co-evolve with SIGLEC14 polymorphisms. Such antibodies also aid in investigating its impact on microbial interactions and tissue damage during chronic inflammation.