Nol3, also known as Nucleolar protein 3 or apoptosis repressor with CARD domain (ARC), is a protein-coding gene. It plays a crucial role in various biological processes, mainly in regulating cell death, such as apoptosis, necroptosis, and pyroptosis [5,8]. It is involved in multiple pathways including JAK-STAT, PI3K-Akt, and apoptotic signaling pathways, which are essential for cell survival, proliferation, and differentiation [1,3,4].

Deletion of Nol3 in mice leads to a myeloproliferative neoplasm (MPN) resembling primary myelofibrosis (PMF), revealing its role as a myeloid tumor suppressor. Nol3-/-MPN mice have an expanded Thy1 + LSK stem cell population with increased cell cycling and myelomonocytic differentiation bias, mediated by JAK-STAT activation and downstream activation of Cdk6 and Myc [1]. In addition, in coronary microembolization-induced myocardial injury, ATXN1L promotes histone H3 deacetylation through HDAC3, thus inhibiting NOL3 expression, and miR-142-3p can attenuate this injury via the ATXN1L/HDAC3/NOL3 axis [2]. In bladder cancer, NOL3 promotes cell proliferation through the PI3K-Akt pathway [3]. In oxidative stress-induced hippocampal neuronal cell death, Tat-NOL3 protects against cell death by regulating apoptotic pathways [4]. In adult granule cell neogenesis in the hippocampus, ARC (encoded by Nol3) plays a critical cell-autonomous role in preventing cell death [5]. A mutation in Nol3 is associated with familial cortical myoclonus, a novel movement disorder [6]. In colorectal cancer, NOL3 is upregulated, and its knockdown suppresses cell proliferation, stemness, and facilitates apoptosis [7].

In conclusion, Nol3 plays essential roles in multiple biological processes such as cell death regulation, cell proliferation, and differentiation. Gene knockout mouse models have been instrumental in uncovering its role in diseases like myeloid malignancies, myocardial injury, bladder cancer, neuronal cell death, and movement disorders. Understanding Nol3 provides insights into disease mechanisms and potential therapeutic targets.