Plants have evolved mechanisms to protect themselves against pathogenic microbes and insect pests. In Arabidopsis, the immune regulator PAD4 functions with its cognate partner EDS1 to limit pathogen growth. PAD4, independently of EDS1, reduces infestation by green peach aphid (GPA). How PAD4 regulates these defense outputs is unclear. By expressing the N-terminal PAD4 lipase-like domain (PAD4 LLD ) without its C-terminal EDS1-PAD4 (EP) domain, we interrogated PAD4 functions in plant defense. Here, we show that transgenic expression of PAD4 LLD in Arabidopsis is sufficient for limiting GPA infestation but not for conferring basal and effectortriggered pathogen immunity. This suggests that the C-terminal PAD4 EP domain is necessary for EDS1-dependent immune functions but is dispensable for aphid resistance. Moreover, PAD4 LLD is not sufficient to interact with EDS1, indicating the PAD4-EP domain is required for stable hetero-dimerization. These data provide molecular evidence that PAD4 has domain-specific functions.