SIGLEC12 (sialic acid-binding immunoglobulin-type lectin 12) is a member of the SIGLEC family of transmembrane receptors that recognize sialic acid-containing glycans. Unlike most SIGLECs, which are primarily expressed in immune cells, SIGLEC12 is found on epithelial cells and is evolutionarily distinct due to a mutation in its sialic acid-binding domain, rendering it unable to bind sialic acid in most humans. Interestingly, a genetic polymorphism allows a subset of the population (~30-40%) to retain a functional SIGLEC12 protein. Research has linked functional SIGLEC12 to chronic inflammation and cancer progression. It is overexpressed in several epithelial cancers (e.g., colorectal, gastric, and prostate cancers), where it appears to promote tumor cell survival, proliferation, and invasion through unclear mechanisms, potentially involving altered immune interactions or intracellular signaling. Antibodies targeting SIGLEC12 have emerged as tools to study its pathological roles and explore therapeutic applications. For instance, anti-SIGLEC12 antibodies can block its pro-tumorigenic signaling or enable targeted drug delivery. Recent studies also suggest its potential as a diagnostic or prognostic biomarker. However, challenges remain in understanding its precise biological functions and optimizing antibody-based strategies, given its unique genetic variability and context-dependent expression in diseases.