AbstractDOCK4, a member of DOCK180 family proteins, was originally identified as a product of a gene deleted during tumor progression. Although its tumor suppression properties have been reported, the regulation mechanism of this protein has not been fully elucidated. DOCK4 shares two conserved domains called as DHR‐1 and DHR‐2 domain as other members including DOCK180. Although DHR‐1 in DOCK180 is reported to bind to PIP3, whether that of DOCK4 exhibits similar function has yet not been examined. In a search for novel PIP3 binding proteins by the PIP3 analog beads binding assay, we found that DOCK4 and its novel splicing variant, whose exon1 and exon52 are different from the known one, bind to PIP3. Binding assay using deletion mutants of DOCK4 revealed that the binding region falls into the DHR‐1 domain. These results raise the possibility that DOCK4 may be regulated by PIP3 to exert its function. © 2008 IUBMB IUBMB Life, 60(7): 467–472, 2008