Hnrnpk, short for heterogeneous nuclear ribonucleoprotein K, is a DNA/RNA-binding protein. It contains 3 K-homologous (KH) domains, mediating nucleic acid binding activity and acting as an enhancer or repressor of gene transcription. Phosphorylation of Hnrnpk can alter its function and serve as a docking platform for signal transduction proteins. It is involved in many cellular events such as lncRNA regulation, cancer development, and bone homeostasis [1].

In mice, deletion of Hnrnpk accelerates the development of post-traumatic and age-dependent osteoarthritis. Mechanistically, Hnrnpk binds and degrades WWC1 mRNA, and its deletion activates the Hippo signaling pathway, aggravating OA [2]. Ablating Hnrnpk in mice causes dwarfism, with damaged survival and premature differentiation of growth plate chondrocytes, due to enhanced transdifferentiation of hypertrophic chondrocytes and increased bone mass, as Hnrnpk deficiency upregulates Hif1α, leading to exorbitant glycolysis [3]. Also, knockdown of Hnrnpk in lung adenocarcinoma (LUAD) cell lines and xenograft mice models suppresses the promoter activity of CLCN3, inhibiting CAFs activation and TGF-β1 production, thus suppressing LUAD progression [4].

In conclusion, Hnrnpk is crucial for maintaining normal biological functions in the skeletal system, especially in cartilage and growth plate chondrocytes. In disease areas, Hnrnpk KO/CKO mouse models have revealed its roles in osteoarthritis and LUAD, highlighting its potential as a therapeutic target in these diseases.