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Phosphoinositide 3 kinase enhancer (PIKE) is a recently identified nuclear GTPase that interacts with nuclear phosphoinositide 3-kinase (PI3 kinase) to stimulate its lipid kinase activity (1). PIKE exists in multiple isoforms; a shorter C-terminal isoform (PIKE-A) has also been identified as centaurin γ 1 (reviewed in 2). The longest isoform (PIKE-L) has been shown to bind to the adaptor protein Homer and thereby link to metabotropic glutamate receptors, leading to activation of PI3 kinase activity and prevention of neuronal apoptosis.3 Overexpression of PIKE-A enhances Akt activity and promotes cancer cell invasion, whereas decreased expression of PIKE-A via dominant negative expression of PIKE-A or PIKE-A knockdown inhibits these processes.4 In many human cancers, expression of PIKE-A is enhanced, leading to increased Akt activity and preventing apoptosis.