NCEH1 (neutral cholesterol ester hydrolase 1) is a serine hydrolase that catalyzes the hydrolysis of cholesterol esters to free cholesterol and fatty acids in macrophages 1. This enzyme plays a critical role in cholesterol homeostasis by generating free cholesterol that is preferentially effluxed from cells via ABC transporters, thereby protecting against foam cell formation 2. NCEH1 is also involved in platelet-activating factor synthesis by hydrolyzing 2-acetyl monoalkylglycerol ether and functions in organophosphate detoxification [UniProt annotation]. In atherosclerosis, NCEH1 expression is dysregulated; elevated NCEH1 promotes cholesterol accumulation in tumor microenvironments and contributes to disease progression 3. NCEH1 is upregulated in pancreatic cancer and associated with poor overall survival 4, while activity-based PET imaging reveals NCEH1 localization at the invasive front of triple-negative breast cancers, suggesting roles in tumor aggressiveness and metastasis 5. Cadmium exposure downregulates NCEH1 expression via miR-30d-5p, disrupting cholesterol homeostasis and promoting atherosclerosis 6. Thus, NCEH1 functions as a dual-role enzyme: protective in atherosclerosis prevention but pathogenic when dysregulated in cancer progression.