Ddx5, also known as p68, is a member of the DEAD-box RNA helicase family. It is involved in multiple aspects of RNA metabolism, such as mRNA processing, miRNA biogenesis, ribosome biogenesis, RNA decay, and long non-coding RNA regulation. It also participates in various cellular signaling pathways, including Wnt/β-catenin signaling, and has implications in maintaining normal physiological functions [3,5,6]. Genetic models, like knockout (KO) and conditional knockout (CKO) mouse models, are valuable for studying its functions.

In keratinocytes, IL-17D-induced inhibition of Ddx5 expression leads to pre-messenger RNA splicing events that favor membrane-bound IL-36R production, amplifying IL-36R-mediated skin inflammation. Mice with keratinocyte-specific deletion of Ddx5 (Ddx5∆KC) are more susceptible to cutaneous inflammation, indicating Ddx5's role in controlling inflammation during skin diseases [1]. In cardiomyocytes, cardiomyocyte-specific deletion of Ddx5 in mice results in heart failure with reduced cardiac function, while overexpression improves cardiac function. Ddx5 regulates the aberrant splicing of CaMKIIδ, preventing the production of CaMKIIδA which impairs Ca²⁺ homeostasis [2]. In chondrocytes, chondrocyte-specific deletion of Ddx5 in a mouse osteoarthritis (OA) model leads to more severe cartilage lesions, as Ddx5 deficiency increases fibrosis and cartilage degradation [4].

In conclusion, Ddx5 plays crucial roles in maintaining normal physiological functions through its involvement in RNA metabolism and signaling pathways. Mouse KO/CKO models have revealed its significance in diseases such as inflammatory skin disorders, heart failure, and osteoarthritis, providing insights into potential therapeutic targets for these conditions.