Background: How cortactin and WASP proteins coordinately regulate branched actin assembly is poorly understood. Results: The Arp2/3 complex-and actin-interacting regions of cortactin and WASP proteins are functionally distinct and tailored to their regulatory roles. Conclusion: Mechanistic distinctions between activators are important in allowing coordinate regulation of branched actin networks. Significance: Understanding mechanistic distinctions between activators is required to understand cellular structures like lamellipodia.