Ddx3x, also known as DBX or DDX3, is a DEAD-box helicase family member. It functions in nearly all stages of RNA metabolism, participating in pathways related to cellular stress response, innate immune response, and metabolic stress response in pancreatic β cells [1]. It is also crucial for embryo development and is closely associated with many well-known molecules. Genetic models, such as KO/CKO mouse models, are valuable for studying its functions.

In hepatocyte-specific Ddx3X knockout (DDX3XΔhep) mice, compared to wild-type control (DDX3Xfl/fl) mice, Ddx3X deficiency leads to significant liver injury in multiple drug-induced liver injury (DILI) models. It aggravates oxidative stress and hepatocyte death by affecting pro-survival stress granule (SG) assembly and induces inflammatory responses with macrophage infiltration, indicating its protective role in DILI [3]. In another study, severe Ddx3x missense mutations in mice disrupt RNA helicase activity, induce ectopic RNA-protein granules in neural progenitors and neurons, and impair translation, uncovering its key role in cortical development and the pathogenesis of Ddx3x-related neurodevelopmental diseases [2].

In conclusion, Ddx3x is essential for RNA metabolism and various biological processes. Model-based research, especially KO/CKO mouse models, has revealed its role in diseases like DILI and neurodevelopmental disorders. Understanding Ddx3x's functions provides insights into disease mechanisms and may guide the development of new therapeutic strategies.