Deciphering the multifunctional role of dual leucine zipper kinase (DLK) and its therapeutic potential in disease.

Dual leucine zipper kinase (DLK, MAP3K12), a serine/threonine protein kinase, plays a key role in neuronal development, as it regulates axon regeneration and degeneration through its downstream kinase. Importantly, DLK is closely related to the pathogenesis of numerous neurodegenerative diseases and the induction of β-cell apoptosis that leads to diabetes. In this review, we summarize the current understanding of DLK function, and then discuss the role of DLK signaling in human diseases. Furthermore, various types of small molecule inhibitors of DLK that have been published so far are described in detail in this paper, providing some strategies for the design of DLK small molecule inhibitors in the future.