HIPK2, short for Homeodomain-interacting protein kinase 2, is an evolutionary conserved serine/threonine kinase [3,4]. It phosphorylates and regulates numerous transcriptional regulators and chromatin modifiers, modulating multiple cellular processes such as apoptosis, DNA damage response, protein stability, and transcription [3,5]. HIPK2 is involved in pathways like Wnt/β-catenin, TGF-β, Notch, NF-κB, and is crucial in various biological processes and disease conditions including cancer, fibrosis, and neurological disorders [1,3,4,5].

In MI, HIPK2 inhibition using HIPK2-/-mice and HIPK2 inhibitor (PKI1H) reduced infarct size and preserved cardiac function during remodeling, suggesting its role in cardiomyocyte apoptosis regulation [2]. In pathological cardiac remodeling, HIPK2 inhibitors (tBID and PKI1H) and HIPK2-/-mice showed improved cardiac function, with HIPK2 inhibition suppressing cardiomyocyte hypertrophy and cardiac fibroblast proliferation and differentiation [7]. In kidney injury, caspase-6-mediated removal of HIPK2's C-terminal region affected NF-κB signaling, and expression of the cleaved HIPK2-CT fragment attenuated renal inflammation in mouse models [6].

In conclusion, HIPK2 plays essential roles in multiple biological processes. Studies using HIPK2 KO mouse models have revealed its significance in diseases such as myocardial infarction, pathological cardiac remodeling, and kidney injury. These findings suggest HIPK2 could be a potential therapeutic target for these disease areas.