KL and hyperinsulinemic hypoglycemia, familial, 4: However, since both, klotho-dependent and klotho-independent signaling, have the same physiologic effect, i.e., to reduce PTH secretion, the biological relevance of klotho-independent signaling is unclear, but it might act as back-up mechanism to ensure FGF23 responsiveness of the parathyroid gland in situations of klotho deficiency.