PTEN is an obligate haplo-insufficient tumor suppressor gene and is commonly mutated in a large number of cancers. It negatively regulates intracellular levels of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) in cells and functions as a tumor suppressor by negatively regulating AKT/mTOR signaling pathway. Approximately 20-30% of colorectal carcinomas involve biallelic inactivation of PTEN through a combination of genetic and epigenetic mechanisms. The R15I missense mutation falls within the PIP2 binding motif in the phosphatase domain of PTEN, which involves residues 6-15. PTEN R15I has been show to result in loss of phosphatase activity in vitro. Clinical trials using PI3K-beta inhibitor are available for patients with PTEN-deficient tumors.