Although the number of studies on the role of Cbl-B and GRAIL in experimental atherosclerosis and human atherosclerotic CVD is limited, these findings, in conjunction with studies from the immunological field, identify Cbl-B and GRAIL as natural brakes on T-cell activation, increasing the expression and/or activity of these E3 ubiquitin ligases may therefore be an attractive strategy to temper T-cell driven inflammation in atherosclerotic CVD. This evidence concerns the gene CBLB and atherosclerosis.