PI3K transduces cell surface activation of receptor tyrosine kinase growth factor and hormone receptors into downstream activation of AKT and other pathways to regulate cell metabolism, size, differentiation, proliferation, migration, and apoptosis.14,15 The PI3K/AKT pathway is constitutively activated in affected tissue from many vascular malformations,1,16,17 primarily through mosaic variation in PIK3CA, as in cancer. Here, PIK3CA is linked to vascular malformation.