B7-H7 (HHLA2) is a newly identified B7 family member that regulates human T-cell functions. B7-H7 was previously known as human endogenous retrovirus-H long terminal repeat associating 2 (HHLA2) with unidentified function. Recently, B7-H7 has been identified as a specific ligand for human CD28H. The B7-H7-CD28H pathway strongly promoted CD4+ T-cell proliferation and cytokine production via an AKT-dependent signaling cascade in the presence of TCR signaling, suggesting B7-H7 comprises a new co-stimulatory pathway. The first IgV domain of B7-H7, which presumably binds to a putative receptor, shows the highest homology to other B7 family members.