HIPK2 in the physiology of nervous system and its implications in neurological disorders

HIPK2 is an evolutionary conserved serine/threonine kinase with multifunctional roles in stress response, embryonic development and pathological conditions, such as cancer and fibrosis. The heterogeneity of its interactors and targets makes HIPK2 activity strongly dependent on the cellular context, and allows it to modulate multiple signaling pathways, ultimately regulating cell fate and proliferation. HIPK2 is highly expressed in the central and peripheral nervous systems, and its genetic ablation causes neurological defects in mice. Moreover, HIPK2 is involved in processes, such as endoplasmic reticulum stress response and protein aggregate accumulation, and pathways, including TGF-β and BMP signaling, that are crucial in the pathogenesis of neurological disorders. Here, we review the data about the role of HIPK2 in neuronal development, survival, and homeostasis, highlighting the implications in the pathogenesis of neurological disorders, and pointing out HIPK2 potentiality as therapeutic target and diagnostic or prognostic marker.