Addressing the mysteries of perforin function.

Perforin is a cytolytic protein stored in secretory granules of CTL and NK cells. It synergizes with proapoptotic serine proteases, granzymes, to deliver the lethal hit to virus-infected or transformed target cells. The mechanism of perforin action has not been described beyond its original characterization in the 1980s, and its role in human disease has remained elusive. This article addresses recent key advances in genetic, clinical and biochemical studies that have reignited the current interest in perforin biology.