GAP1IP4BP is a member of the GAP1 family of Ras GTPase-activating proteins (Ras GAPs) that includes GAP1m, CAPRI, and RASAL. Composed of a central Ras GAP domain, surrounded by amino-terminal C2 domains and a carboxyl-terminal pleckstrin homology/Bruton’s tyrosine kinase domain, GAP1IP4BP has previously been shown to possess an unexpected GAP activity on the Ras-related protein Rap, besides the predicted Ras GAP activity (Cullen, P. J., Hsuan, J. J., Truong, O., Letcher, A. J., Jackson, T. R., Dawson, A. P., and Irvine, R. F. (1995) Nature 376, 527–530). Here we have shown that GAP1IP4BP is indeed an efficient Ras/Rap GAP, having Kms of 213 and 42 μM and estimated kcats of 48 and 16 s−1 for Ras and Rap, respectively. For this dual activity, regions outside the Ras GAP domain are required, as the isolated domain (residues 291–569) retains a pronounced Ras GAP activity yet has very low activity toward Rap. Interestingly, mutagenesis of the Ras GAP argi-nine finger, and surrounding residues important in Ras binding, inhibit both Ras and Rap GAP activity of GAP1IP4BP. Although the precise details by which GAP1IP4BP can function as a Rap GAP remain to be determined, these data are consistent with Rap associating with GAP1IP4BP through the Ras-binding site within the Ras GAP domain. Finally, we have established that such dual Ras/Rap GAP activity is not restricted to GAP1IP4BP. Although GAP1m appears to constitute a specific Ras GAP, CAPRI and RASAL display dual activity. For CAPRI, its Rap GAP activity is modulated upon its Ca2+-induced association with the plasma membrane.