Cholesterol efflux from macrophage foam cells, a key step in reverse cholesterol transport,
requires trafficking of cholesterol from intracellular sites to the plasma membrane.
Sphingomyelin is a cholesterol-binding molecule that transiently exists with cholesterol in
endosomes and lysosomes but is rapidly hydrolyzed by lysosomal sphingomyelinase (L-
SMase), a product of the acid sphingomyelinase (ASM) gene. We therefore hypothesized
that sphingomyelin hydrolysis by L-SMase enables cholesterol efflux by preventing …