Hyperinsulinemia activates the insulin receptor substrate 1 (IRS1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/Akt) pathways, which deactivate Akt substrate 160 (AS160) through Ser/Thr phosphorylation and subsequently reduce the downstream inhibition of Rab GTPase activating proteins (Rabs) (47). The gene discussed is IRS1; the disease is hyperinsulinism.