NAA50 is the catalytic subunit of the NatE N-alpha-acetyltransferase complex, functioning as a co-translational protein modifier with broad substrate specificity 1. It acetylates the N-terminus of proteins retaining their initiating methionine, except those with proline at the second position, and can acetylate all MXAA peptides except MPAA 1. NAA50 associates with NAA10 and NAA15 to form NatE complexes, which collectively contribute to major N-terminal acetylation at the ribosome exit tunnel 1. NAA50 negatively regulates NAA10 acetylation activity through structural alteration of substrate-binding sites 2. Beyond protein acetylation, NAA50 exhibits serotonin N-acetyltransferase activity and participates in melatonin biosynthesis 3. NAA50 is essential for sister chr3 cohesion during mitosis by promoting CDCA5/sororin binding to cohesin, potentially counteracting NAA10 function 4. Pan-cancer analysis reveals NAA50 is overexpressed in most cancers with significant prognostic implications, correlating with increased MDSC infiltration and reduced T cell/NK infiltration; knockout studies demonstrate NAA50 promotes cell proliferation in lung adenocarcinoma 5. NAA50 also displays lysine-ε-acetyltransferase activity with unclear physiological relevance 2.