Hipk1, short for Homeodomain interacting protein kinase 1, is a conserved serine/threonine kinase belonging to the CMGC superfamily [3,4]. It interacts with homeobox proteins and other transcription factors, acting as a transcriptional co-regulator, and is involved in multiple biological processes such as signal transduction, apoptosis, and cellular proliferation in response to various extracellular stimuli [3]. It is also associated with pathways like p53 signaling [4]. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable for studying Hipk1's functions.

In pathological cardiac hypertrophy, both genetic ablation of Hipk1 and gene therapy targeting it protect against pathological hypertrophy and heart failure in vivo. Hipk1 inhibition prevents phenylephrine-induced cardiomyocyte hypertrophy by inhibiting cAMP-response element binding protein (CREB) phosphorylation at Ser271 and inactivating CCAAT/enhancer-binding protein β (C/EBPβ)-mediated transcription of pathological response genes [1]. In acute lung injury (ALI) in an LPS-induced mouse model, interference of Hipk1 by siRNA attenuated inflammation and oxidative stress indicators and enhanced autophagy [2].

In conclusion, Hipk1 is a key regulator in multiple biological processes. Studies using KO/CKO mouse models have revealed its significant role in pathological cardiac hypertrophy and acute lung injury. These findings suggest that targeting Hipk1 could be a potential therapeutic strategy for treating related diseases [1,2].