Altogether, these results demonstrate the oncogenic nature of ERAS in mammary and other epithelial cells, highlight the importance of ERAS in epithelial pathophysiology, and open up the possibility that alterations in the expression of ERAS could be the causative agent of some of the syndromes of the PIK3CA-related overgrowth spectrum or of some RASopathies with unknown genetic cause. The gene discussed is PIK3CA; the disease is RASopathy.