Nceh1, or Neutral Cholesterol Ester Hydrolase 1, is an enzyme involved in ether lipid metabolism and plays a critical role in regulating cholesterol ester metabolism [1,2,3]. It is associated with pathways related to cell-cell adhesion junctions, pancreatic cancer, and other cancer-associated pathways [1]. Genetic models, especially knockout mouse models, are valuable for studying its function.

In diet-induced diabetic mice, deficiency of Nceh1 impairs endothelial function, as it disrupts the dissociation of endothelial nitric oxide synthase (eNOS) from caveolin-1 (Cav-1), leading to reduced eNOS activation and nitric oxide (NO) release [3]. In macrophages, absence of Nceh1 augments 25-hydroxycholesterol-induced ER stress and apoptosis, due to defective hydrolysis of 25-HC ester in the endoplasmic reticulum [4]. Also, loss of Nceh1 in bone marrow-derived cells aggravates atherosclerosis, which can be attenuated by the loss of ACAT1, an enzyme that esterifies free cholesterol to cholesteryl esters [5].

In conclusion, Nceh1 is essential for maintaining normal endothelial function, preventing macrophage apoptosis induced by oxysterols, and modulating atherosclerosis development. The study of Nceh1 knockout mouse models has provided insights into its role in diabetes-related endothelial dysfunction and atherosclerotic diseases [3,4,5].