Surfaceome nanoscale organization and extracellular interaction networks

•The surfaceome is a complex signaling gateway enabling extracellular interactions.•Surfaceome PPI’s are modulated by proteoform composition, abundance and their respective nanoscale organization.•Advanced chemoproteomic technologies are needed to gain new insights into the functional surfaceome signaling network.•Insighst into surfaceome nanoscale organisation will inform the design of multitarget drugs.