Possible models for the manner in which JEM mutations may alter receptor processing. (A) By placing the HD-LNR complex away from the membrane, conformational changes allow for increased cleavage of S2. (B) One or several membrane-linked X-factor(s) lend additional stability to the HD-LNR complex that is lost in JEM mutants due to the increased distance of the HD-LNR complex from the membrane. Professional illustration by Debra T. Dartez.