Foamy macrophage generation is based on an imbalance favoring modified LDL influx and endogenous lipid synthesis over free cholesterol efflux and lipid catabolism.[33] Given that i) modulating HM13/SPP expression did not impact HDL‐mediated cholesterol efflux, free cholesterol levels, or known atherosclerosis‐associated cholesterol metabolism genes and ii) HM13/SPP is an aspartic intramembrane protease linked to cholesterol‐dependent ERAD,[34] we reasoned that HM13/SPP likely promotes endogenous lipid synthesis through an ERAD‐based mechanism. The gene discussed is HM13; the disease is atherosclerosis.