In the rather rare genetic disease Netherton Syndrome (NS), which is found in about 1 of 200,000 newborns, SPINK5 mutations cause the loss of functional LEKTI-1, leading to uncontrolled KLK activation, excessive corneodesmosome degradation, skin barrier collapse, and inflammation via PAR-2 signaling [207]. The gene discussed is F2RL1; the disease is Netherton syndrome.