CD5 is a cluster of differentiation found on a subset of IgM-secreting B cells called B-1 cells, and also on T cells.B-1 cells have limited diversity of their B-cell receptor due to their lack of the enzyme terminal deoxynucleotidyl transferase (TdT) and are potentially self-reactive. CD5 serves to mitigate activating signals from the BCR so that the B-1 cells can only be activated by very strong stimuli (such as bacterial proteins) and not by normal tissue proteins. CD5 was used as a T-cell marker until monoclonal antibodies against CD3 were developed.

In humans, the gene is located on the long arm of chromosome 11. There is no ligand confirmed, even if CD72, a C-type lectin, may be considered a probable ligand.

T cells express higher levels of CD5 than B cells. CD5 is upregulated on T cells upon strong activation. In the thymus, there is a correlation with CD5 expression and strength of the interaction of the T cell towards self-peptides.

Function: May act as a receptor in regulating T-cell proliferation. CD5 interacts with CD72/LYB-2.