HIPK3 is a serine/threonine protein kinase that functions as a transcriptional regulator with pleiotropic roles in cellular signaling. As a kinase, HIPK3 phosphorylates key transcription factors including JUN and RUNX2, modulating their transcriptional activity 1. In steroidogenesis, HIPK3 phosphorylates NR5A1 to activate SF1, promoting steroidogenic gene expression via cAMP signaling [UniProt]. HIPK3 negatively regulates apoptosis by phosphorylating FADD and suppressing JUN kinase activity, thereby controlling cell survival pathways [UniProt]. Beyond the linear protein product, HIPK3 generates abundant circular RNA (circHIPK3) with independent regulatory functions 2. CircHIPK3 acts as a competitive endogenous RNA, sponging microRNAs to regulate cellular proliferation and viability 1. Dysregulation of HIPK3 is implicated in multiple human diseases including cancers, cardiovascular disease, diabetes mellitus, and kidney injury/regeneration 31. HIPK3 protein stability is regulated by WWP1-mediated ubiquitination and degradation, representing a critical post-translational control mechanism in cancer progression 4. In kidney regeneration, SOX9 modulates HIPK3 expression in tubular epithelial cells, suggesting involvement in injury response 5.