Lipid droplet-associated hydrolase (LDAH)

Lipid droplet-associated hydrolase (LDAH) is an evolutionarily conserved serine hydrolase abundantly expressed in macrophages, adipose tissue, liver, and other tissues with active lipid storage. LDAH localizes to lipid droplets (LDs), structures specialized for storing neutral lipids such as triglycerides and cholesterol esters. Its core functions include mobilizing esterified sterols from LDs, promoting cholesterol efflux, and, paradoxically, stimulating accumulation of triglycerides by enhancing lipid droplet fusion, size, and biogenesis. Mechanistically, LDAH antagonizes ATGL (adipose triglyceride lipase) by enhancing its polyubiquitination and proteasomal degradation, which results in reduced TAG hydrolysis and increased storage. In the context of disease, particularly atherosclerosis, LDAH expression in macrophages facilitates a beneficial shift toward cholesterol efflux, a less inflammatory phenotype, and more stable atherosclerotic plaques. The protein does not appear to be directly targeted by drugs, but is used as a research tool to understand pathways of lipid storage and mobilization.

Other names

Lipid droplet-associated hydrolaseLDAHC2orf43hLDAHFLJ21820Lipid droplet-associated serine hydrolaseUPF0554 protein C2orf43

Not applicable for direct modulatory drugs; functional antagonism with ATGL (adipose triglyceride lipase): LDAH promotes TAG storage in part by increasing proteasomal degradation of ATGL. Modulates hydrolysis/mobilization of cholesterol esters and regulatory sterols. Increases triglyceride accumulation through effects largely independent of its canonical hydrolase motif, suggesting a role in lipid droplet dynamics.