The PI3K-AKT pathway is activated rarely by hotpot mutations in the Pik3ca, which encodes the catalytic subunit of the lipid phosphatase PI3K, or in genes encoding the serine-threonine kinases Akt1 or Akt3. The PI3K-AKT pathway can also be activated in melanoma by loss of expression or function of the tumor suppressor PTEN, which is a lipid phosphatase that counteracts PI3K and regulates this pathway. The gene discussed is AKT1; the disease is melanoma.