{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNAA15 serves as the essential auxiliary subunit of the NatA complex, partnering with the catalytic subunit NAA10 (also known as hARD1) to mediate co‐translational N‑terminal acetylation of nascent polypeptides. This modification regulates multiple aspects of protein biology—including stability, folding, complex assembly, subcellular targeting, and degradation—and is achieved by NAA15 enhancing the substrate recognition and ribosome–enzyme interactions of the NatA complex. Structural and biochemical studies have further revealed that specific metazoan domains of NAA15 facilitate high‐affinity binding to regulatory proteins such as HYPK and modulate the association of additional catalytic units, thereby fine‑tuning acetyltransferase activity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic studies have underscored the importance of NAA15 in human development. Variants in NAA15 have been linked to a spectrum of neurodevelopmental disorders characterized by varying degrees of intellectual disability, speech and motor delays, autism spectrum disorder, and craniofacial dysmorphism. Furthermore, alterations in NAA15 have been associated with congenital cardiac anomalies including arrhythmias and hypertrophic cardiomyopathy. These observations, corroborated by in vitro and in vivo functional assays as well as by clinical exome sequencing, emphasize that haploinsufficiency or missense changes in NAA15 can disrupt NatA function and lead to developmental and multisystem defects."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its developmental roles, aberrant NAA15 expression has been observed in various cancers. Overexpression of the NatA complex—including its NAA15 subunit—has been reported in thyroid carcinomas and is linked to altered acetylation patterns that affect cell cycle regulation and apoptosis. Moreover, siRNA‑mediated knockdown studies indicate that reduced NAA15 levels destabilize NAA10 and impair NatA activity, resulting in enhanced apoptosis and increased sensitivity to chemotherapeutic agents. Complementary proteomic and biochemical analyses have further established that NAA15 is integral to proper NAT activity, even extending to multifunctional roles such as N-terminal propionylation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Thomas Arnesen, Dave Anderson, Christian Baldersheim, et al. 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