Gelsolin activity is tightly regulated by calcium ions and phosphatidylinositol 4,5-bisphosphate (PIP2). In the absence of calcium, gelsolin remains in an inactive state. Upon calcium binding, gelsolin undergoes a conformational change that activates its actin-severing and capping functions. PIP2 can bind to gelsolin, inhibiting its actin-severing activity, thus providing another layer of regulatory control.