The Src family of protein tyrosine kinases (Src-PTKs) is important in the regulation of growth and differentiation of eukaryotic cells. The activity of Src-PTKs in cells of different types is negatively controlled by Csk. Csk binding protein (Cbp), also designated phosphoprotein associated with glycosphingo-lipid-enriched microdomains (GEMs) or PAG, is a ubiquitously expressed transmembrane phosphoprotein that binds specifically to the SH2 domain of Csk. Cbp is involved in the membrane localization of Csk and in Csk-mediated inhibition of c-Src. In the plasma membrane, Cbp is exclusively localized in the GM1 ganglioside-enriched detergent-insoluble membrane domain, which is important in receptor-mediated signaling. Cbp is a component of the regulatory mechanism controlling the activity of membrane-associated Src-PTKs.