HM13 and early-onset autosomal dominant Alzheimer disease: Signal peptide peptidase (SPP) is a member of a larger group of intramembrane cleaving proteases (I-CLiP) that play a variety of important roles in cell signaling [1] and regulation [2], cell surveillance [3], intracellular communication [4], Alzheimer's disease [5], cancer [6,7], and hepatitis C virus [8].