Pdcd5, also known as programmed cell death protein 5, is a member of the programmed cell death protein family. It is involved in multiple biological processes, including cell proliferation, apoptosis, cell cycle progression, and is associated with several signaling pathways such as p53, TGF-β1/Smad, and HDAC3-related pathways [1,2,6,7,8]. Pdcd5 is of great biological importance as it may act as a tumor suppressor gene and is related to the regulation of fibrosis, immune cell development, and the prognosis of certain diseases [2,3,4,5,6,7]. Genetic models, especially KO/CKO mouse models, play a crucial role in studying its functions.

In hepatocellular carcinoma, Lgr5 can bind to Pdcd5, blocking its nuclear translocation and leading to p53 degradation, thus inducing doxorubicin resistance [1]. In cardiac fibrosis, PDCD5 is upregulated by SMAD3, which in turn inhibits HDAC3 to reduce fibrotic responses [2]. In renal cell carcinoma, PDCD5 is downregulated, and its re-expression can regulate cell proliferation and T cell activation through the HDAC3/miR-195-5p/SGK1 axis [5]. In osteosarcoma, PDCD5 inhibits metastasis by attenuating EMT through the TGF-β1/Smad signaling pathway [7]. In iNKT cell development, mice with T cell-specific deletion of PDCD5 have decreased numbers of thymic and peripheral iNKT cells with maturation defects and abolished iNKT1 lineage due to reduced T-bet expression [4].

In conclusion, Pdcd5 is a key regulator in multiple biological processes and disease conditions. Studies using KO/CKO mouse models have revealed its significant roles in cancer chemoresistance, cardiac fibrosis, immune cell development, and tumor metastasis. Understanding Pdcd5's functions provides potential therapeutic targets for treating related diseases.