Human CD38 is a non-lineage restricted surface molecule which acts as a multi-functional ectoenzyme involved in the regulation of cytosolic calcium. Besides its enzymatic activity, the molecule performs as a receptor, playing a role in activation, differentiation, apoptosis and implementation of specific programs, such as cytolysis, induction of cytokines, activation of kinases and phosphorylation of discrete proteins. CD38 is also crucial in the modulation of cell/cell interactions, as was highlighted in different environments (lymph nodes, blood vessels, bone marrow, etc.). These observations suggested that CD38 may serve as a receptor for surface ligands and one was recently identified as CD31. Other molecules that share significant structural and functional homology with CD38 have been identified in human, mouse and rat. The finding that the genes for all these structures are synthenic and located in the same region (4p l5 in human) suggest the existence of a new family of related proteins. Studying the role of CD38 in pathological conditions such as myeloma, X-linked agammaglobulinemia and HIV infection may provide clues to the function of the molecule in vivo and its potential use in diagnosis and therapy.