CD45 has been identified as a transmembrane glycoprotein, broadly expressed among hematopoietic cells. Multiple isoforms of CD45 are distributed throughout the immune system according to cell type. These isoforms arise because of alternative splicing of exons 4, 5 and 6. The corresponding protein domains are characterized by the binding of monoclonal antibodies specific for CD45RA (exon 4), CD45RB (exon 5), CD45RC (exon 6) and CD45RO (exons 4 to 6 spliced out). The variation in these isoforms is localized to the extracellular domain of CD45, while the intracellular domain is conserved. CD45 functions as a phosphotyrosine phosphatase, a vital component for efficient tyrosine phosphorylation induction by the TCR/CD3 complex. The tyrosine phosphatase activity of CD45 is contained within the conserved intracellular domain. Src and Syk family protein tyrosine kinases are utilized by the TCR/CD3 complex to initiate signaling cascades. Several members of these two families, including Lck, Fyn and ZAP-70, have been implicated as physiological substrates of CD45.