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Theranostics 2021; 11(10):4759-4769. doi:10.7150/thno.54072 This issue Cite

Review

MLKL: Functions beyond serving as the Executioner of Necroptosis

Chaoning Zhan^*, Minchun Huang^*, Xiaojun Yang^✉, Jin Hou^✉

Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, P.R. China.
*These authors contribute equally to this work.

✉ Corresponding authors: Jin Hou and Xiaojun Yang. Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou Da Dao Bei 1838, 510515, Guangzhou, P.R. China. E-mail address: houjinedu.cn (Jin Hou) or yxj_dencom (Xiaojun Yang) More

Abstract

Recently, necroptosis, as a programmed cell death pathway, has drawn much attention as it has been implicated in multiple pathologies, especially in the field of inflammatory diseases. Pseudokinase mixed lineage kinase domain-like protein (MLKL) serves as a terminal-known obligate effector in the process of necroptosis. To date, the majority of research on MLKL has focused on its role in necroptosis, and the prevailing view has been that the sole function of MLKL is to mediate necroptosis. However, increasing evidence indicates that MLKL can serve as a regulator of many diseases via its non-necroptotic functions. These functions of MLKL shed light on its functional complexity and diversity. In this review, we briefly introduce the current state of knowledge regarding the structure of MLKL, necroptosis signaling, as well as cross-linkages among necroptosis and other regulated cell death pathways, and we particularly highlight recent progress related to newly identified functions and inhibitors of MLKL. These discussions promote a better understanding of the role of MLKL in diseases, which will foster efforts to pharmacologically target this molecule in clinical treatments.

Keywords: MLKL, necroptosis, structure, inhibitors, therapeutic target.

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