Signalling through the ErbB family of receptor tyrosine kinases and their EGF-related ligands is involved in many aspects of development and has been implicated in tumorigensis. Regulation of ErbB signalling occurs at many levels. On p. 4557 Fedor Berditchevski and co-workers report that the metastasis suppressor CD82, a transmembrane protein of the tetraspanin family, negatively regulates EGF-induced signalling through the receptor EGFR (also known as ErbB1) by attenuating its ligand-induced dimerisation with ErbB2. In a sucrose density gradient analysis of cellular lysates from mammary epithelial cells, the researchers show that CD82 expression increases EGFR and ErbB2 concentrations in the light fractions, indicating that CD82 expression induces a change in compartmentalisation of EGFR in lipid microdomains on the surface membrane. Furthermore, in CD82-expressing cells the ganglioside GD1a colocalises with EGFR and CD82. The researchers conclude that CD82 modulates EGFR signalling by altering its compartmentalisation and that this process is mediated by GD1a.