ToxStrategies scientists have published an article proposing an oral reference dose (RfD) for the per‐ and polyfluoroalkyl substance (PFAS) commonly known to as GenX. The new proposed value differs from those put forth by many regulatory agencies. The assessment relies on mechanistic data to show that many of the effects observed in rodents involve PPARa, which is well recognized to exhibit differential responses in rodents and humans. Using updated histopathological nomenclature, liver effects in mice that were previously scored as necrosis were more accurately scored as apoptosis (i.e., programmed cell death)—which is consistent with involvement of PPARa. With this new insight, the ToxStrategies assessment evaluates and synthesizes the available toxicity data for GenX and uses frequentists and Bayesian benchmark dose (BMD) modeling methods to derive both deterministic and probabilistic RfD values that are protective of noncancer effects. The open-access article appears in the Journal of Applied Toxicology. A video abstract of this article (produced by Research Square) can be found here.