The ORMDL (ORM1-like) family of proteins consist of ORMDL1, ORMDL2 and ORMDL3 that may play roles in gamma-secretase complex maturation. Localized to the membrane of the endoplasmic reticulum, ORMDLs are widely expressed and are implicated in the expression of Presenilin (PSI) which is involved in Alzheimer’s disease (AD). Expression of ORMDL1 is down-regulated in PSI mutations, suggesting a possible role as a therapeutic target for AD. ORMDLs have recently been identified as a potential risk factor for childhood asthma.