Zc3h14, encoding a zinc finger CCCH-type containing protein, is an evolutionarily conserved RNA-binding protein. It is involved in multiple RNA-related processes, such as RNA processing, and is associated with pathways like integrin signaling. It has significant biological importance, especially in the context of male fertility, neuronal function, and cancer [1-5]. Genetic models, like knockout mice, are valuable for studying its functions.

In knockout studies, Zc3h14-/-mice exhibit disrupted spermatogenesis and reduced testicular circRNA levels, revealing its role in male fertility through modulating backsplicing for circRNA biogenesis [1]. In Drosophila, mutation of the Zc3h14 ortholog dNab2 impairs axon projection in the developing brain and short-term memory, indicating a conserved role in neurons [3]. In mice, Zc3h14Δex13/Δex13 mice show enlarged lateral ventricles, impaired working memory, and dysregulation of synaptic proteins, highlighting its role in proper brain function [4]. In HCC, downregulation of Zc3h14 driven by chromosome 14q31 deletion promotes cancer progression by activating integrin signaling [2].

In conclusion, Zc3h14 plays essential roles in male fertility, neuronal development and function, and cancer development. Studies using knockout models, especially in mice, have provided crucial insights into its functions in these specific disease-related biological processes. These findings contribute to a better understanding of the underlying mechanisms and may offer potential therapeutic targets for related diseases.