The vast number of precise intercellular connections within vertebrate nervous systems is only partly explained by the comparatively few known extracellular guidance cues. Large families of neural orphan receptor proteins have been identified and are likely to contribute to these recognition processes but due to the technical difficulty in identifying novel extracellular interactions of membrane-embedded proteins, their ligands remain unknown.
Söllner, C., & Wright, G. J. (2009). A cell surface interaction network of neural leucine-rich repeat receptors. Genome Biology, 10(9). https://doi.org/10.1186/gb-2009-10-9-r99