Naa20, also known as N-α -acetyltransferase 20, is the catalytic subunit of the NatB complex. NatB is responsible for N -terminal acetylation of approximately 20% of the human proteome, a process crucial for protein homeostasis, localization, and interactions [2,3,4]. This modification is involved in multiple biological pathways and is linked to various human diseases [3]. Genetic models such as yeast and mouse models have been instrumental in studying Naa20's functions [7,6].

In triple-negative breast cancer (TNBC), knockdown of Naa20 in TNBC cells significantly inhibited cell viability, migration, and invasion. Naa20 promoted TNBC progression by regulating Rab5A-mediated activation of EGFR signaling, as Naa20 knockdown decreased EGFR expression, internalization, and degradation, and down-regulated PI3K, AKT, and mTOR phosphorylation. In a xenograft mouse model, Naa20 knockdown suppressed tumor growth [1]. In hepatocellular carcinoma (HCC), Naa20 promoted oncogenic properties. It inhibited the LKB1-AMPK-mTOR axis through its N-terminal acetyltransferase activity, contributing to cell proliferation and autophagy [5]. In NatB-deficient mouse embryonic fibroblasts (Naa20 -/-), reduced responsiveness to an extrinsic pro-apoptotic stimulus was observed, and NatB was found to protect procaspase-8 from UBR4-mediated degradation [6].

In conclusion, Naa20, as a key component of the NatB complex, plays essential roles in protein N-terminal acetylation. Model-based research, especially KO mouse models, has revealed its significance in diseases like TNBC and HCC, and in apoptosis regulation. Understanding Naa20's functions provides potential therapeutic targets for related diseases [1,5,6].