XPO5, also known as Exportin 5, is a key protein in miRNA biogenesis. It mediates the nuclear export of precursor pre-miRNA to the cytoplasm in a RanGTP-dependent manner, which is crucial for miRNA maturation and their subsequent function in gene expression regulation, thus maintaining cell homeostasis [1,2]. The XPO5/RAN-GTP complex is involved in the miRNA processing system, and its altered expression is linked to cancer risk [3].

Genetic deletion of XPO5 in mouse models compromises the biogenesis of most miRNAs, leading to severe defects during mouse embryonic development and skin morphogenesis, revealing its physiological functions in development [2]. In head and neck squamous cell carcinoma (HNSCC) cell lines, knockdown of XPO5 by siRNA decreased cell proliferation, delayed wound healing, and increased caspase-3 enzyme activity, suggesting an oncogenic role of XPO5 in HNSCC [4]. In hepatocellular carcinoma (HCC), XPO5 was downregulated, and its overexpression suppressed cell proliferation and tumorigenicity, while knockdown promoted migration, indicating a tumor-suppressive role in HCC [5].

In conclusion, XPO5 is essential for miRNA biogenesis and has a significant impact on development and disease. Mouse models and in vitro knockdown experiments have revealed its role in cancer, such as in HNSCC and HCC, highlighting its potential as a biomarker and therapeutic target in these disease areas.