Phagocytic complement C1q receptor (C1qRp) and thrombomodulin (TM, CD141), are two key members of a novel family of lectin receptors involved in cell-cell interactions and innate immune host defense. We report here that the mouse homologue of human C1qRp (AA4) and TM are derived from a common ancestor on the basis that both genes co-localized to the same region of the chromosome 2 and also because they share similar domain composition and organization. Moreover, we found that mouse AA4 was localized to sites known to express TM. Mouse AA4 was identified by Western blot as a heavily glycosylated protein (110 kDa) expressed in all tissues tested. Brain and spleen expressed an additional 130-kDa band. Immunoperoxidase and double-immunofluorescence experiments showed that, surprisingly, the major site of AA4 expression in all tissue tested is on endothelial cells and that despite the apparent involvement of AA4 in the phagocytic response, it is not expressed by tissue macrophages. In contrast, megakaryoblasts (in bone marrow and spleen) and platelets expressed abundant levels of AA4 stored in cytoplasmic vesicles. Interestingly, alveolar epithelial cells (lung) but not other epithelia (e.g. uterus) were strongly stained for AA4. Although AA4 has been described on all hematopoietic progenitors, we found that only circulating immature B cells, monocytes and NK cells but not T cells and neutrophils expressed AA4.