Perforin is a cytolytic mediator produced by killer lymphocytes, and is stored in and released by cytoplasmic granules. The proteh is partiall, homologous to the terminal components of the membrane attack complex of complement and produces pores of up to 20 nm in diameter on target membranes. Its genomic and protein structures hail recenth beer1 14s raveled, and its function elucidated through the azuilahility of geneticaIl> engineered, perforin-deficient mice. Here Chau-Ching 1. il-I. Craig M. W&h and John Ding-E Young briefly outline certain biochemical and molecular features of perforin, and discuss the still-evolving issues concerning the relezlance of perforin and Fas in cell killing.

Over the past two decades, immunologists have strenLI-ously attempted to decipher the molecular basis of lymphocyte-mediated cytotoxicity. Two models have been proposed:‘granule exocytosis/pore formation” and ‘internal disintegration’2. The former model gained the most support following the identification of several mediators present within the cytoplasmic granules of killer lymphocytes such as cytolytic T lymphocvtes (CTLs) and natural killer (NK) cells. One pore-for&g protein named perforin (also known as PFP, cytol?-sin and CS-related protein) has been particularly well characterized3mh. However, although this model appears attractive, its physiological significance has long been questioned. Recent biochemical and molecular hiological studies involving perforin may have reconciled some of the issues under debate.