Pdcd5, short for programmed cell death 5, is a member of the programmed cell death protein family. It is ubiquitously expressed in tissues and is involved in multiple biological processes such as apoptosis, cell cycle regulation, and cell proliferation. Pdcd5 has been shown to interact with key signaling pathways like the p53 pathway, playing a crucial role in determining cell fate decisions [5,8,9].

In hepatocellular carcinoma, Lgr5 can bind to Pdcd5, blocking its nuclear translocation and leading to p53 degradation, which in turn causes doxorubicin resistance [1]. In cardiac fibrosis, PDCD5 is upregulated by SMAD3 and ameliorates fibrosis by inhibiting HDAC3 [2]. In rheumatoid arthritis, increased Pdcd5 expression is linked to the incidence and remission of the disease, making it a potential biomarker [3]. In iNKT cell development, mice with T cell-specific deletion of Pdcd5 have decreased numbers of thymic and peripheral iNKT cells and defects in iNKT1 lineage development [4]. In renal cell carcinoma, downregulation of Pdcd5 is observed, and its re-expression can regulate cell proliferation and T cell activation [6]. In osteosarcoma, Pdcd5 overexpression inhibits cell adhesion, migration, invasion, and angiogenesis by attenuating EMT through the TGF-β1/Smad signaling pathway [7]. In p53-dependent human colon cancer cells, STK31 interacts with Pdcd5 to maintain its stability and promote apoptosis [8].

In conclusion, Pdcd5 is a multifunctional gene involved in apoptosis, cell cycle, and cell proliferation regulation. Its dysregulation is associated with various diseases including cancers, cardiac fibrosis, and rheumatoid arthritis. Studies using gene-knockout models in mice have been instrumental in revealing its role in these biological processes and disease conditions, providing potential therapeutic targets for these diseases.