At present, the mechanism(s) and pathway(s) by which extracellular Trx1 influences cellular behavior remain unknown. As many of its reported extracellular activities depend on a functional active site, it appears likely that Trx1 catalyzes thiol-disulfide exchange in one or more cell surface target proteins through its enzymatic activity. However, thiol-disulfide exchange reactions, even if highly specific, are too transient to be detected by conventional techniques. To date, only a single cell surface receptor, CD4, a member of the immunoglobulin superfamily, has been shown to be susceptible to Trx1 redox activity (Matthias et al, 2002) . Other cell surface proteins targeted by the enzymatic activity of Trx1 await identification.