Neuropilin, you gotta let me know: should I stay or should I go?

Neuropilins are highly conserved single pass transmembrane proteins specific to vertebrates. They were originally identified as adhesion molecules in the nervous system, but were subsequently rediscovered as the ligand binding subunit of the class 3 semaphorin receptor in neurons and then as blood vessel receptors for the vascular endothelial growth factor VEGF. More recently they have also been implicated as mediators of the T-cell immune response and as key prognostic markers in several types of cancer. Because neuropilins bind multiple ligands and associate with several different types of co-receptors, they variably promote cell adhesion, repulsion or attraction. Which response they ultimately invoke is decided by the cellular and even subcellular context the neuropilins find themselves in. Here, we review how the developmental functions of the neuropilins are influenced by such different contexts.