IQGAP1 can regulate actin polymerization by at least three different mechanisms. A) RGCT domain of IQGAP1 can Cdc42 or Rac1 is recruited by autoinhibited WASp through ‘Cdc42-interactive-binding’ (CRIB) motif. This causes a conformational change in the C-terminal verprolin homology domain and central acidic (VCA) region of WASp allowing globular actin to bind through an electrostatic steering mechanism. In addition, IQGAP1 transiently protects Cdc42-GTP in its activated state, reducing its GTP hydrolysis. By delaying the hydrolysis of WASp-bound Cdc42-GTP, IQGAP1 stabilizes the VCA domain of WASp. This sustains the interaction with Arp2/3 and globular actin, promoting the polymerization and branching of actin. B) The CH domain of IQGAP1 interacts with polymerized F-actin. a single N-terminal CH domain facilitates actin polymerization by cross linking filaments into interconnected bundles. C) RGCT domain of IQGAP1 can regulate polymerized actin filament through myosin light chain (MLC) in a co-ordinated effort of MLC kinase and MLC phosphatase by PAK and Rho, respectively. In addition, MLC kinase function can be regulated by IQGAP1-bound calmodulin.