The present invention relates to VSTM5-specific antibodies, antibody fragments, and VSTM5 polypeptides, conjugates and compositions comprising same, for modulating (antagonizing or agonizing) one or more of the effects of VSTM5 expression on immunity. More specifically, the present invention relates to VSTM5-specific antibodies, antibody fragments, and VSTM5 polypeptides, conjugates and compositions comprising same for treating and aiding in the diagnosis of cancer, infectious diseases and immune related diseases, e.g., those associated with aberrant (higher or lower than normal) VSTM5 expression by diseased and/or immune cells and/or aberrant (increased or reduced) VSTM5-mediated effects on immunity.