CD299. also known as CLEC4M or L-SIGN (Liver/lymph node-Specific ICAM-3 Grabbing Non-integrin), is a C-type lectin receptor primarily expressed on liver sinusoidal endothelial cells and lymph node endothelial cells. It plays a role in pathogen recognition, immune regulation, and cell adhesion by binding high-mannose glycans on viral envelopes and bacterial surfaces. CD299 interacts with pathogens such as HIV, Ebola, hepatitis C virus (HCV), and Mycobacterium tuberculosis, facilitating their capture and presentation to immune cells. Structurally, it contains a carbohydrate recognition domain (CRD) critical for glycan binding and a transmembrane region enabling signal transduction. Antibodies targeting CD299 are valuable tools for studying its role in infections, immune tolerance, and inflammatory diseases. They help elucidate mechanisms of pathogen entry, immune evasion, and potential therapeutic interventions. Additionally, CD299 antibodies have diagnostic applications, such as detecting receptor expression in tissues or blocking pathogen-receptor interactions in experimental models. Research also explores their utility in vaccine development and targeted therapies, particularly for liver-tropic infections. Understanding CD299’s dual role in immunity and infection continues to drive antibody-based research in infectious and autoimmune diseases.