With resistance to current frontline antimalarials spreading globally, new drug candidates need to be discovered to populate the antimalarial drug development pipeline. We previously screened the Medicines for Malaria Venture Pathogen Box for compounds that prevent Plasmodium falciparum parasites from exiting and invading human erythrocytes, steps essential for the proliferation of parasites in the blood, which causes disease. Compound MMV020512 (M-512) was identified in this screen and live cell imaging here established that it does not specifically inhibit invasion but probably generally inhibits parasite growth. M-512 resistance selection in parasites led to the identification of mutations in the membrane protease PfROM8 and the cation ion channel PfCSC1. PfROM8 was validated as a target of M-512 when a L562R putative resistance mutation was engineered into wildtype parasites reproducing a strong resistance phenotype. Knockdown of wildtype PfROM8 and the L562R mutant reduced parasite growth, indicating that the protein is functionally important. Counterintuitively, the PfROM8 knockdown parasites became more resistant to M-512 suggesting that the compound is an agonist of PfROM8 and that over-activation of the protein is deleterious to parasite growth.