Entamoeba histolytica, the protozoan parasite responsible for amoebiasis, deploys a complex array of virulence factors to establish infection and evade host defenses. Here, we identify KERP2 as a dual-function effector that regulates both parasite homeostasis and host cell remodeling. Interactome of KERP2 with host epithelial cells was identified by co-immunoprecipitation on Caco-2 cells post interaction with HA-KERP2 expressing E. histolytica.