HIPK1 is a serine/threonine-protein kinase involved in transcription regulation and TNF-mediated cellular apoptosis. It plays a role as a corepressor for homeodomain transcription factors and phosphorylates homeodomain transcription factors. Among its substrates, it phosphorylates DAXX in response to stress, mediating DAXX translocation from the nucleus to the cytoplasm, and it inactivates the transcription factor MYB by phosphorylation. It also phosphorylates PAGE4 at Thr-51, which is critical for the ability of PAGE4 to potentiate the transcriptional activator activity of JUN.

In the absence of TNF, HIPK1 prevents MAP3K5-JNK activation. TNF triggers its translocation to the cytoplasm in response to stress stimuli, which relieves repression, activates nuclear MAP3K5-JNK signalling and promotes apoptosis. HIPK1 may also be involved in anti-oxidative stress responses. Further roles reported in the annotation include regulation of eye size, lens formation and retinal lamination during late embryogenesis, promotion of angiogenesis, and involvement in erythroid differentiation. It may be involved in malignant squamous cell tumour formation.

The HIPK1 gene encodes a member of the CMGC Ser/Thr protein kinase family, HIPK subfamily, and belongs to the homeodomain interacting protein kinase family alongside HIPK2 and HIPK4. The protein is found in the nucleus, including nuclear speckles, and in the cytoplasm. Alternative splicing of the HIPK1 gene results in four transcript variants encoding four distinct isoforms. Orthologs are designated Hipk1 in both mouse and rat. Researchers may also encounter the older names KIAA0630, Myak and Nbak2 in the literature.