@article{10.1172/JCI134333, author = {Marsha Wills-Karp}, journal = {The Journal of Clinical Investigation}, publisher = {The American Society for Clinical Investigation}, title = {At last — linking ORMDL3 polymorphisms, decreased sphingolipid synthesis, and asthma susceptibility}, year = {2020}, month = {2}, volume = {130}, url = {https://www.jci.org/articles/view/134333}, pages = {604-607}, abstract = {Asthma is a common chronic respiratory disease that has a heritable component. Polymorphisms in the endoplasmic reticular protein orosomucoid-like protein 3 (ORMDL3), which regulates sphingolipid homeostasis, have been strongly linked with childhood-onset asthma. Despite extensive investigation, a link between ORMDL3 asthma–risk genotypes and altered sphingolipid synthesis has been lacking. In this issue of the JCI, Ono et al. establish a clear association between nonallergic childhood asthma, lower whole-blood sphingolipids, and asthma-risk 17q21 genotypes. These results demonstrate that genetic variants in ORMDL3 may confer a risk of developing childhood asthma through dysregulation of sphingolipid synthesis. As such, modulation of sphingolipids may represent a promising avenue of therapeutic development for childhood asthma.}, number = {2}, doi = {10.1172/JCI134333}, url = {https://doi.org/10.1172/JCI134333}, }