Nα-terminal acetylation (NTA) ranges among the most abundant protein modifications in higher eukaryotes. Over 40 % of the human and plant proteome are co-translationally acetylated by a single Nα-acetyltransferase (Nat) termed NatA. The core NatA complex consists of the catalytic subunit NAA10 and the ribosome-binding subunit NAA15. In humans, the regulatory subunit HYPK and the acetyltransferase NAA50 join the complex. Even though both are conserved in Arabidopsis thaliana, only AtHYPK is known to interact with AtNatA. Here we analyse the interactome of AtNAA50 and provide evidence for the association of the enzyme with AtNatA. Moreover we demonstrate that AtNAA50 interacts with ribosome-associated proteins involved in protein translation, folding and translocation. A recent study shows that acetylation protects NatA substrates from proteasomal degradation. In consequence, NatA depletion results in an accelerated protein turnover. We report that this is not true for the depletion of AtNAA50, suggesting that the enzyme is not required for NatA activity. In line with this, novel amiNAA50 knockdown lines do not display the characteristic drought resistance of NatA mutants. Instead, complementary transcriptome and proteome analyses suggest that AtNAA50 is a negative regulator of plant immunity. Pathogen challenges confirm that amiNAA50 plants are resistant to oomycetes and bacteria.