MD-2 in mouse atherosclerotic lesions can carry cholesterol to activate TLR4 signaling and regulate chronic inflammation in atherosclerosis.[114–116] Inhibition of MD-2 could prevent TNF-α and IL-6 production and reduce nuclear localization of the NF-κB p65 subunit in macrophages to improve atherosclerosis lesions.[117] To date, other known ligand-receptor costimulatory molecules, which played functional roles in cardiovascular atherosclerotic disorders, have been reported, including B7-H3/TLT-2, B7-H5/CD28H, and B7-H6/NKp30. The gene discussed is TREML2; the disease is atherosclerosis.