Perforin and granzyme pathway

The Perforin and granzyme pathway is a central mechanism by which cytotoxic lymphocytes—such as cytotoxic T cells and natural killer cells—induce apoptosis in virus-infected cells and tumor cells. The process involves two main components: perforin, a pore-forming protein that creates channels in the target cell membrane; and granzymes, a family of serine proteases that enter the target cell through these pores. Once inside the target cell cytoplasm, granzymes cleave specific substrates to trigger programmed cell death pathways such as caspase activation. This highly specific killing mechanism ensures minimal damage to surrounding healthy tissues while efficiently eliminating abnormal cells. Recent research has also highlighted alternative mechanisms for granzyme entry into target cells via receptor-mediated endocytosis independent of perforin pores. The canonical model remains that perforin facilitates efficient delivery of granzymes into the cytosol where they execute their apoptotic functions. The Perforin and granzyme pathway is essential for immune defense against viral infections and cancer but can also contribute to pathological conditions like graft-versus-host disease when dysregulated.

Other names

Granule exocytosis pathwayCytotoxic lymphocyte-mediated apoptosis pathwayPerforin/granzyme-dependent cell death pathway

Inhibition of perforin or granzymes to block cytotoxic lymphocyte-mediated apoptosis; potential use as immunosuppressants in transplantation or autoimmunity