It was particularly surprising that the neural tube defects associated with HAI-2-deficiency were unrelated to either excessive or reduced (through desensitization) PAR-2 activity, despite the unequivocal contribution of PAR-2 signaling to neural tube closure, and the wealth of strong circumstantial evidence that prostasin and matriptase contribute to PAR-2 activation in this process [45], [65]. This evidence concerns the gene ST14 and hyperinsulinemic hypoglycemia, familial, 4.