Agollah GD et al. reported that mutations in the INPPL1 gene encoding SHIP-2 lead to hyperactivation of PI3K/AKT signaling, which is negatively regulated by SHIP-2 to mediate various forms of lymphedema, due to reduced LEC proliferation, adhesion, migration, and lumen formation (Agollah et al., 2014). Here, PIK3CA is linked to lymphedema.