While the role of HIPK2 in cancer is well described elsewhere [for example in the following reviews [7], [8], [9], [10]], here we review the molecular and functional interplay among HIPK2 and key neurological signaling pathways, pointing out its physiological role in nervous system development and homeostasis, and its potential involvement in neurological disorders, including neurodegenerative diseases. This evidence concerns the gene HIPK2 and neurodegenerative disease.