Gnl3l, also known as Guanine nucleotide-binding protein-like 3-like protein, is an evolutionarily conserved GTP-binding nucleolar protein [2]. It belongs to the HSR1-MMR1 subfamily of GTPases [5]. Gnl3l is involved in multiple cellular processes. It participates in regulating cell proliferation and is associated with pathways such as AMPK, NF-κB, ATM/p53, and is crucial for cell cycle regulation [1,3,4].

In esophageal cancer, Gnl3l overexpression promotes cell viability, proliferation, and autophagy via regulating the AMPK signaling pathway. Silencing Gnl3l in KYSE410 cells shows opposite phenotypes [1]. In acute myeloid leukemia, Gnl3l acts as a poor prognostic factor, enhancing RELA activity, activating NF-κB, promoting cell proliferation, resisting apoptosis, and encouraging cytarabine resistance [4]. In chronic obstructive pulmonary disease (COPD), knockdown of Gnl3l in a CS/LPS-induced mouse model and cigarette smoke extract-induced human bronchial epithelial cells significantly improves pathological features, promotes cell viability, and inhibits inflammation, oxidative stress, and the ATM/p53 pathway [3].

In conclusion, Gnl3l plays significant roles in cell proliferation, autophagy, and cell cycle regulation. The findings from gene-knockdown studies in disease-relevant models, like esophageal cancer, acute myeloid leukemia, and COPD, highlight its importance in these disease conditions, potentially serving as a therapeutic target for these diseases.