We here report on the identification of a novel human EGF-TM7 receptor, designated EMR4. Like most EGF-TM7 receptor genes, EMR4 is localized on the short arm of chromosome 19, in close proximity to EMR1. Remarkably, due to a one-nucleotide deletion in exon 8, translation of human EMR4 would result in a truncated 232-amino acid protein lacking the entire seven-span transmembrane region. This deletion is not present in nonhuman primates, including chimpanzees, suggesting that EMR4 became nonfunctional only after human speciation, about five million years ago. Thus, EMR4 surprisingly accounts for a genetic difference between humans and primates related to immunity.