A substantial body of research has established that pathogenic mutations in the presenilin 1 (PS1) and presenilin 2 (PS2) genes underlie most familial Alzhemer's disease (FAD: [6]), and that PS1 or PS2 forms the catalytic site of the γ-secretase aspartyl proteinase complex [7]. The gene discussed is PSEN1; the disease is familial Alzheimer disease.