HIPK1 is a serine/threonine protein kinase that functions as a transcriptional regulator involved in stress response and apoptosis. The kinase phosphorylates multiple substrates including p53, c-Myb, and DAXX 1 2, acting as a corepressor of homeodomain transcription factors. In TNF-mediated apoptosis, HIPK1 translocates from the nucleus to cytoplasm upon stress stimuli, thereby derepressing MAP3K5-JNK signaling and promoting apoptosis 3. HIPK1 regulates cardiac homeostasis by phosphorylating CREB at Ser271; HIPK1 inhibition prevents pathological cardiac hypertrophy through suppression of CREB-C/EBPβ signaling in response to hypertrophic stress 4. The kinase influences developmental processes, including eye development and angiogenesis 3. Clinically, HIPK1 has relevance to multiple diseases: gene-targeted HIPK1-knockout mice showed reduced susceptibility to carcinogen-induced skin tumors, suggesting a role in tumorigenesis through p53/Mdm2 regulation 1. HIPK1 was identified as a conserved longevity gene in mice and validated in Caenorhabditis elegans 5. Recent evidence indicates HIPK1 may function as a regulatory kinase for CHD7 in cardiac development 6. HIPK1 expression is regulated by miR-22, with HIPK1 suppression improving recombinant protein expression 7.