Despite the major biological importance of perforin as a mediator of antiviral and anticancer immunity, the cis regulatory elements on mouse or human chromosome 10 that control perforin gene (PRF1) expression have long eluded our understanding. In a recent study of near-Herculean proportions, Pipkin, Lichtenheld and colleagues at the University of Miami have now defined both the functional boundaries of human PRF1, and identified the probable locus control region that bestows both cell lineage- and IL-2- and TCR-specific gene expression.