Calcineurin (CN), a calcium- activated phosphatase, plays a critical role in various biological processes including T cell activation. Cabin1, a calcineurin binding protein 1, has been shown to bind directly to CN using its C-terminal region and inhibit CN activity. However, no increase in CN activity has been found in Cabin1 Delta CT cells, which produce a truncated Cabin1 lacking the C-terminal CN binding region. Here, we report that Cabin1 has additional CN binding domain in its 701-900 amino acid residues. Cabin 1 (701-900) blocked both CN-mediated dephosphorylation and nuclear import of NFAT and thus inhibited IL-2 production in response to PMA/ionomycin stimulation. This fact may explain why Cabin1 Delta C mice previously showed no significant defect in CN-mediated signaling pathway. (C) 2007 Published by Elsevier Inc.