By constructing a reporter mouse strain that allows for ex vivo monitoring of cellular APOB lipoprotein uptake and combining this with single-cell RNA sequencing (scRNA-seq) and deletion experiments, we reveal that KCs dominate the liver response through secretion of atherosclerosis-modulating factors but also by restraining circulating APOB lipoprotein levels. The gene discussed is APOB; the disease is atherosclerosis.