The ORMDL (ORM1-like) family of proteins consist of ORMDL1, ORMDL2 and ORMDL3; all of which are human homologs of the S. cerevisiae ORM1 protein. Localized to the membrane of the endoplasmic reticulum, ORMDLs are multi-pass membrane proteins that are implicated in ?secretase (BACE) function, as well as expression of Presenilin (PSI), a protein involved in Alzheimer disease (AD). ORMDL1 (ORM1-like protein 1), also known as Adoplin-1, is a widely expressed 153 amino acid member of the ORMDL family. Expression of ORMDL1 is down-regulated in PSI mutations, suggesting a possible role as a therapeutic target for AD. ORMDL2 (ORM1-like protein 2), also known as Adoplin-2, and ORMDL3 (ORM1-like protein 3) are expressed in tissues such as heart, brain, lung, liver and kidney. ORMDL3 exists as two isoforms due to alternative splicing events and may be a determinant of susceptibility to childhood asthma