Determining the biological consequences of the thousands of genetic variants that contribute to common diseases is challenging. Genetic variants that influence autoimmune diseases have been identified in the gene encoding TYK2 (tyrosine kinase 2), but conflicting evidence regarding their biological impact obscures the therapeutic potential of TYK2. In resolving this conflict, Dendrou et al. have revealed a genetic effect that drives an optimal degree of immune signaling: low enough to be protective against autoimmunity but high enough to prevent immunodeficiency. These findings indicate that TYK2 may be a potential drug target in a number of autoimmune conditions.
