Macrophages are a heterogeneous population of immune cells that fulfill essential functions in the defense against pathogens as well as the maintenance of tissue integrity and remodeling of tissues. However, errant macrophages pose a serious threat to the organism as a whole as they can either fuel inflammation in chronic inflammatory disorders or block effective immune surveillance in the tumor microenvironment. This heterogeneity complicates effective therapy, as indiscriminative targeting of macrophages leads to severe side effects in tissue homeostasis or fighting infections. Folate receptor beta (FR), a GPI anchored protein that is selectively expressed in activated macrophages, was proposed as a promising marker of harmful macrophage populations. To further investigate the applicability of FR, we characterized the protein microenvironment of FR to identify interacting proteins for use in bispecfic targeting of specific macrophage subpopulations and utilized this proteomic information to decipher the function of FR. As a result of this strategy, we detected FR-proximal proteins, which can be utilized to discriminate functionally diverse macrophage populations. More importantly, we detected a functional interaction between FR and the integrin heterodimer CD11b/CD18. This interaction changes the conformation of CD11b/CD18 and regulates adhesion to collagen in FR-transduced THP-1 cells and human primary macrophages. Further, we found that FR-expressing cells display a reduced ability to migrate through collagen-rich matrixes and thereby identified FR as a novel regulator of macrophage homing.