Ormdl sphingolipid biosynthesis regulator 3

The ORMDL family, whose name stands for ORM1 (Saccharomyces cerevisiae)–like genes,^[8] consists of three members (ORMDL1-3) which are localised in the membrane of the endoplasmic reticulum (ER).^[9] All three human ORMDL genes encode 153 amino acid products.^[9] The genes ORMDL1, ORMDL2 and ORMDL3 are located on human chromosomes 2q32, 12q13.2 and 17q21, respectively.^[8]

ORMDL3 negatively regulates de novo sphingolipid synthesis through interaction with serine palmitoyltransferase (SPT),^[9][10] but it may be present in relative excess of SPT physiologically, as ORMDL3 overexpression does not significantly reduce cellular sphingolipid biosynthesis.^[11] ORMDL3 also has a role in regulating Ca²⁺ levels in the endoplasmic reticulum.^[12] The ER is very important for generation, signaling function and storage of intracellular Ca²⁺. There are channels, which control the exit of Ca²⁺ from the ER into the cytoplasm and also pumps (sarco-endoplasmic reticulum Ca²⁺ ATPase or SERCA) which return Ca²⁺ back to the ER.^[13] Dysregulation of Ca²⁺ has the key role in several pathological conditions like dysfunction of SERCA, asthma,^[14] and Alzheimer's.^[15]

Mutations in ORMDL3 are associated with inflammatory diseases like Crohn's disease, type 1 diabetes,^[16] and rheumatoid arthritis.^[17]