ICAM4 is an intercellular adhesion molecule and Landsteiner-Wiener blood group antigen encoded on chromosome 19 1. Functionally, ICAM4 serves as a receptor ligand for integrin complexes, mediating cell-cell adhesion through interactions with macrophage (ITGAX:ITGB2) and platelet (ITGA2B:ITGB3) integrins, and promoting erythrophagocytosis 1. The protein is a component of the erythrocyte membrane 2 and is expressed on red blood cells alongside other adhesion molecules 3. Genetically, ICAM4 displays population-specific variation; seven distinct alleles derived from the ancestral LW*05 allele have been identified through SNPs in Caucasian and African American populations 1. Clinically, ICAM4 variants are implicated in multiple disease contexts. Genetic variation in the ICAM1-ICAM4-ICAM5 locus is associated with systemic lupus erythematosus (SLE) susceptibility across multiple ancestries through an integrin-mediated pathway 4. Additionally, DNA methylation of ICAM4 participates in uterine fibroid formation via regulation of immune cell infiltration 5, and ICAM4 variants show association with gastroschisis risk 6. ICAM4 has also emerged as a proteomic biomarker for cardia gastric cancer diagnosis 7, demonstrating its broader relevance beyond blood group antigenicity.