PTEN is a candidate tumor suppressor gene mapping to the homozygous deletion on human chromosome 10q23. It appears to be mutated at considerable frequency in human cancers. The predicted PTEN protein has a protein tyrosine phosphatase domain and extensive homology to tensin. Studies have shown that purified PTEN catalyzes dephosphorylation of PtdIns(3,4,5)P3, specifically at position 3 on the inositol ring, and raise the possibility that PTEN acts in vivo as a phosphoinositide 3-phosphatase by regulating PtdIns(3,4,5)P3 levels. PTEN has been implicated in a large number of human tumors and is conserved from humans to worms. Characterization of PTEN protein showed that it is a phosphatase that acts on proteins and on 3-phosphorylated phosphoinositides, and can therefore modulate signal-transduction pathways that involve lipid second messengers. Recent results indicate that at least part of its role is to regulate the activity of the serine/threonine kinase AKT/PKB, and thus influence cell survival signaling. Although PTEN has the consensus sequence of a protein tyrosine phosphatase, it dephosphorylates p-nitrophenylphosphate and other synthetic and protein substrates poorly. The greatest catalytic activity has been observed with the highly negatively charged, multiply phosphorylated polymer of (Glu-Tyr)n.