Tumor protein D52-like proteins (TPD52) are small coiled-coil motif bearing proteins that were first identified in breast carcinoma. Three human TPD52 members had been identified, named hD52 (TPD52), hD53 (TPD52L1), and hD54 (TPD52L2). The most important characteristic of the protein family is a highly conserved coiled-coil motif that is required for homo- and heteromeric interaction with other TPD52-like proteins. TPD52 and related proteins have been implicated in cell proliferation, apoptosis, and vesicle trafficking. TPD52L2 has five isoforms produced by alternative splicing, and its multiple sites have been identified to be phosphorylated. Interaction of TPD52L2 with MAL2, a novel member of the MAL proteolipid family, may be required for the role of TPD52L2 in vesicle transport.