Leucine-rich glioma inactivated 4 (LGI4) protein is another candidate ligand for ADAM22 receptor. Schwann cells secrete LGI4, which through binding to the axonal receptor ADAM22 drives axonal ensheathment and myelination in the peripheral nervous system (PNS) but not central nervous system. LGI4 secretion defect results in inability of Schwann cells to correctly myelinate peripheral nerves, resulting in peripheral nervous system hypomyelination and the murine claw-paw phenotype (Birmingham et al. 2006). LGI4 interacts with not only ADAM22 but also interacts moderately with ADAM11 and ADAM23 (Ozkaynak et al. 2010, Sagane et al. 2008, Nishino et al. 2010).