The transmembrane protein tyrosine phosphatase CD148 is expressed on numerous cell types, including most cells of the hematopoietic lineage. CD148 has been shown to regulate density-dependent inhibition of cell growth as well as cellular differentiation in nonhematopoietic cells and has been shown to regulate signal transduction processes in several nonlymphoid hematopoietic cell types. Analysis of CD148 expression on lymphoid cells has demonstrated that CD148 is expressed at low levels on T cells and that it is upregulated in response to activation. Several groups have observed that CD148 negatively regulates T cell activation in response to crosslinking of the T cell antigen receptor, suggesting that it may play a role in feedback inhibition of the T cell immune response. In the B cell compartment, CD148 expression appears to be restricted to the memory subpopulation, raising the possibility that it serves a unique function in these cells, which has yet to be determined. Recent studies have shown that CD148 interacts with the PDZ domain-containing protein syntenin, raising the possibility that its function or its localization with substrates in T and B cells may be controlled through this or a related interaction with another PDZ domain protein.