Abstract The loss or decline of vertebrate frugivores can limit the regeneration of plants that depend on them. However, empirical evidence is showing that this is still very scarce, as functionally equivalent species may contribute to maintain the mutualistic interaction. Here, we investigated the long-term consequences of the extinction of frugivorous lizards on the population persistence of a Mediterranean relict shrub Cneorum tricoccon (Cneoraceae). We examined the demographic parameters among 26 insular and mainland populations, which encompass the entire plant distributional range, comparing populations with lizards with those in which these are extinct, but in which alien mammals currently act as seed dispersers. Plant recruitment was found to be higher on island populations with lizards than on those with mammals, and the long-term effects of the native disperser's loss were found in all vital phases of plant regeneration. The study thus gives evidence of the cascading effects of human-induced changes in ecosystems, showing how the disruption of native ecological processes can lead to species regression and, in the long term, even to local extinctions.