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Germinal center kinases (GCKs) form a large part of the mammalian Ste20 kinase family. GCKs are involved in a variety of signaling pathways governing multiple biological processes including cell cycle, apoptosis, proliferation, cytoskeleton reorganization, cell polarity and migration, cell volume and ion transport. Dysregulation of GCKs has been linked to cell malfunction and human diseases. Despite the physiological and pathological importance of GCKs, the activation and regulatory mechanisms of their kinase activities are not fully understood. Moreover, GCK centered signaling network remains incomplete. This review highlights latest research progress on the biological functions and structures of GCKs by individual subfamilies, hoping to provoke insights into new ideas of GCK cell biology.