Fig. 3. A model for the role of twinfilin in actin filament turnover. ADF/cofilin feeds new monomers to the cytoplasmic pool by depolymerizing actin filaments at their minus-ends. Because twinfilin binds ADP-actin-monomers with a high affinity and through an overlapping interface with ADF/cofilin, it may sequester actin monomers from ADF/cofilin. Twinfilin inhibits the spontaneous nucleotide exchange on actin monomers and may localize actin monomers, in their inactive ADP-form, to the sites of rapid actin filament assembly. The localization of twinfilin to the sites of rapid actin filament assembly is mediated through interactions with capping protein. After localization, the ADP-actin-monomer is released from twinfilin and subsequent nucleotide exchange and assembly into the plus-end of the filament may be catalyzed by profilin. The activities of cofilin, profilin and twinfilin are downregulated by phosphatidylinositol 4,5-bisphosphate (PI(4,5)P₂).