The phosphorylation of tyrosine residues is an essential element of many signal transduction pathways triggered by hormones, mitogens, and oncogenes that lead to processes such as cell growth, proliferation, and differentiation. Protein phosphorylation is reversible and controlled by the opposing action of protein kinases and phosphatases that catalyze phosphorylation and dephosphorylation, respectively. In our work, we will investigate the crystal structure of a representative member of the receptor-like protein tyrosine phosphatase, namely, human PTPu, using X-ray diffraction techniques. This is particular interisting in light of the observation that the extracellular portion of PTPu, which is reminiscent of the extracellular portion of neural cell adhesion molecules (N-CAMs), participates in forming homophilic binding interactions. It is possible that signals resulting from cell-cell contacts may be transduced across the plasma membrane resulting in modulation of the catalytic activity of PTPu. It is of interest to understand the structure of PTPu which would provide insight into the structural mechanism of transmembrane signal transduction.