A novel protein, designated Presenilin 1 (also designated S182) and mapping to the AD3 locus of chromosome 14q24.2, has been described. Mutations in PSEN1, the gene encoding Presenilin 1, have been found in families suffering from early-onset Alzheimer’s disease. A highly related protein, designated Presenilin 2 (also designated STM2), shares 80% amino acid sequence identity with Presenilin 1. Presenilin 1 and 2 have similar structures and represent novel members of the seven-pass transmembrane receptor superfamily. Point mutations in the gene encoding Presenilin 2 have been found in Volga German families who suffer from an inherited form of early-onset Alzheimer’s disease. Whether these proteins function as ligand-gated ion channels or G protein-coupled receptors has yet to be resolved. ALG-3, the mouse homolog of human Presenilin 2, has been cloned from the mouse liver cDNA library.