Germinal center kinases (GCKs; EC 2.7.11.1) are a family of ‘Sterile 20 (STE20) like kinases’, that regulate cell proliferation and apoptosis upon extracellular stimuli. They are mitogen-activated protein kinase (MAPK) kinase kinase kinases that are termed MAP4Ks and function as upstream activators of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway and to a lesser extend of the p38 MAPKs signaling pathway[1]. MAP4K2 is reported to play an essential role in pathogen-associated molecular pattern signaling and systemic inflammation. Upon pathogen-associated molecular pattern stimulation, MAP4K2 can form a complex with tumor-necrosis factor receptor associated factor 6 and mixed lineage protein kinase 3, which stabilize MAP4K2 to activate JNK/p38 for competent innate immune response[2].