Presenilin 1 (PS1) and presenilin 2 (PS2), derived from PSEN1 and PSEN2, first identified as genes mutated in families with familial Alzheimer’s disease (FAD) (Cruts et al., 1996), form the catalytic component of the γ-secretase complex (Steiner, 2008; Li et al., 2009). The gene discussed is PSEN2; the disease is familial Alzheimer disease.