MAP kinase kinase kinase kinases (MAP4Ks) belong to the mammalian STE20-like family of serine/threonine kinases. Four members of the family (MAP4K1/HPK1, MAP4K2/GCK, MAP4K3/GLK or KHS2 and MAP4K5/KHS1) are included in this KHS subfamily, whilst the fifth member (MAP4K4/HGK) resides in the MSN subfamily. The functions of the MAP4Ks in immunity and inflammation are reviewed by Chuang et al. (2016) [1]. MAP4Ks have been identified as therapeutic targets for amyotrophic lateral sclerosis (ALS) [2].

Inhibiting MAP4Ks preserves motor neurons in an ALS mouse model [2].

1. Chuang HC, Wang X, Tan TH. (2016) MAP4K Family Kinases in Immunity and Inflammation. Adv Immunol, 129: 277-314. [PMID:26791862]

2. Liu ML, Ma S, Tai W, Zhong X, Ni H, Zou Y, Wang J, Zhang CL. (2024) Screens in aging-relevant human ALS-motor neurons identify MAP4Ks as therapeutic targets for the disease. Cell Death Dis, 15 (1): 4. [PMID:38177100]