The IL-6 family of cytokines mediates functions in host protective immunity, development of multiple organs, tissue regeneration and metabolism. Inborn errors in cytokines or cytokine receptor units highlight specific roles for IL-6, IL-11, LIF, OSM, and CLC signaling. Gp130 encoded by IL6ST is the common cytokine receptor chain of the IL6 cytokine family. Genetic variants in IL6ST cause a spectrum of phenotypes highlighting diverse biological mechanisms.