Nacc1, or Nucleus accumbens-associated protein 1, is a member of the BTB/POZ protein families. It functions mainly as a transcription co-regulator, forming homo-or hetero-dimers through the BTB/POZ or BEN domain with other transcriptional regulators to regulate downstream signals. Nacc1 is involved in various biological processes such as embryonic development, stem cell pluripotency, and innate immunity, and is associated with diseases, especially cancers [1].

A missense mutation in Nacc1 (c.892C>T, p.Arg298Trp) causes severe neurodevelopmental delay. Engineered Nacc1+/R284W mouse models showed delayed weight gain, epileptiform discharges, behavioral seizures, and hindlimb clasping. RNA-seq revealed over 1,000 differentially expressed genes in the cortex of P14 mutant mice, with glial transcripts downregulated and synaptic genes upregulated [2]. In acute myeloid leukemia (AML), Nacc1 is highly expressed. Lentiviral-mediated knockdown of Nacc1 inhibited the PI3K/AKT signaling pathway, promoted apoptosis, suppressed proliferation, and caused cell cycle arrest in AML cells. Nacc1 also regulated ADAM9 expression in AML cells [3]. In nasopharyngeal carcinoma (NPC) cell lines, Nacc1 expression was upregulated. Silencing Nacc1 inhibited cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) by inhibiting the AKT/mTOR signaling pathway [4].

In conclusion, Nacc1 plays a crucial role in multiple biological processes and diseases. Mouse models with Nacc1 mutations have provided valuable insights into its functions in neurodevelopmental disorders and cancer. Understanding Nacc1 can offer new perspectives on the mechanisms of these diseases and potential therapeutic targets.