(Top) A model of the molecular mechanisms by which two actin isoforms may segregate to different actin networks. On the left, a system carrying wild‐type actin is able to generate both the branched and linear‐actin networks. On the two central panels, defective interactions of an actin isoform with one or several ABPs affect branched‐ or linear‐network assembly. On the right, combining these two actin variants in one cell should trigger a natural segregation of actins and rescues the wild‐type actin organization. (Bottom) Effect of perturbing an actin assembly pathway for cells using one or two actin variants. On the left, when one actin is shared for two actin functions, the inhibition of one actin assembly pathway (e.g., branched networks with CK‐666) leads to a reinforcement of the other actin assembly pathway. On the right, when two actin variants are used for two different actin functions, this effect is limited as both actin networks assemble more independently. In other words, having a system with two actin variants can buffer against the addition of the drug.