Although CTLs are equipped with other mechanisms of cytotoxicity, the perforin/granzyme pathway is key for human CTL and natural killer cell effector function, as indicated by the immunodeficiency status and the alteration of immune homeostasis in patients with genetic mutations of perforin or of molecules implicated in lytic granule docking and fusion to plasma membrane18, 19. Here, PRF1 is linked to immunodeficiency disease.