In mouse models with overexpression of the serine/threonine kinase AKT3, a downstream target of the PI3K pathway, Zboray et al. found that AKT3 overexpression led to ACC with 100% penetrance, while reversal of its expression could revert the phenotype, suggesting a potential therapeutic target in preclinical models [74]. The gene discussed is PIK3CA; the disease is adrenal cortex carcinoma.