YARS1 and tyrosinemia: This study shows that tyrosine is an endogenous negative regulator of TyrRS levels, providing a potential molecular basis for the decreased protein synthesis in the AD brains31–34, tyrosine-mediated cognitive impairments8,9 and inhibition of protein synthesis38,39, axonal degeneration in tyrosinemia patients10, increased oxidative DNA damage and mutations in aged and AD neurons50, and the circadian modulation of synaptic TyrRS (Supplementary Fig. 7a)49.