Ddx6, also known as Rck/p54, is a member of the DEAD-box family of helicases highly conserved from unicellular eukaryotes to vertebrates. It is an essential component of cytoplasmic RNA-processing bodies (P-bodies) and plays a crucial role in multiple post-transcriptional processes such as mRNA storage, translational repression, and decay [3]. It is also involved in pathways like miRNA-mediated gene silencing, alternative translation initiation, and RNA editing [3,7]. In addition, Ddx6 has been implicated in the regulation of cell fate transitions, stress granule and P-body assembly, and immune-related regulatory networks, making it a key player in maintaining cellular homeostasis [1,2,4]. Genetic models, especially knockout (KO) and conditional knockout (CKO) mouse models, are valuable tools for studying its functions.

Suppression of Ddx6 in human and mouse primed embryonic stem cells endows them with a differentiation-resistant, “hyper-pluripotent” state and enables easy reprogramming to a naive state [1]. In adult progenitors, Ddx6 controls the balance between self-renewal and differentiation in a context-dependent manner [1]. Ddx6-silencing in non-immune cells suppresses the NF-κB pathway and inhibits activation of the IL-6 amplifier, while its overexpression enhances NF-κB promoter activity, suggesting its involvement in the pathogenesis of inflammatory diseases [5]. In pancreatic cancer, compared with adjacent tissues, Ddx6 expression is abnormally increased in human pancreatic cancer tissues, and overexpression promotes cancer cell proliferation and tumor formation, while knockdown has the opposite effects [6].

In conclusion, Ddx6 is a multifunctional regulator in post-transcriptional gene expression. Studies using KO/CKO mouse models have revealed its significance in cell fate determination, stress response, and the pathogenesis of inflammatory and cancerous diseases. Understanding Ddx6's functions provides insights into biological processes and may offer potential therapeutic targets for related diseases.