To make things even more complicated, there are four isoforms in the class I PI3K family: PI3Kα/β are ubiquitously expressed and often abnormally activated in cancer cells by constitutively activated PI3KCA mutations or loss-of-function PTEN mutations, while PI3Kδ/γ are commonly restricted to leukocytes and essential for immune surveillance. The gene discussed is PTEN; the disease is cancer.