The KCNJ11 gene functions in insulin secretion by encoding the Kir6.2 subunit of an ATP-sensitive potassium channel in pancreatic beta-cells.  Activating mutations inhibit closing of the channel, which can prevent insulin secretion and lead to insulin-dependent neonatal diabetes with median age of onset six weeks.  Some patients are affected with additional features of developmental delay (20%) and epilepsy (6%), which is called DEND syndrome in its severe form. KCNJ11 mutations account for approximately half of permanent neonatal diabetes and a small proportion of transient cases that resolve in early childhood but may relapse years later. Oral sulfonylurea drug therapy is an effective alternative to insulin for diabetics with KCNJ11 mutations.  Family history of affected patients is usually negative as the majority of KCNJ11 mutations are de novo in this condition. Inactivating mutations of KCNJ11 result in excessive insulin secretion and cause approximately 5% of congenital hyperinsulinism cases.  Presentation with symptoms related to persistent hypoglycemia varies from severe neonatal onset with seizures and hypotonia through mild episodes later in infancy or early childhood.  Congenital hyperinsulinism occurs in a diffuse form, generalized throughout the pancreas, which may be treated with pancreatic resection, and a focal form, limited to a single or small number of hyperplastic areas of the pancreas which can be targeted for selective surgical removal.  Most KCNJ11-related hyperinsulinism does not respond well to diazoxide treatment.