Adaptation to Amino Acid Availability: Role of GCN2 in the Regulation of Physiological Functions and in Pathological Disorders**The authors have equally participated to this work.

In mammals, nine amino acids are qualified as essential (EAA) since they cannot be synthesized endogenously and thus must be supplied by the food. Therefore, complex mechanisms execute a fine control of amino acid homeostasis in the case of a dietary protein/EAA scarcity. Part of this regulation involves the modulation of the expression of numerous genes and physiological functions. This review outlines the signaling mechanisms that underline the control of gene expression by EAA limitation. Particularly, we will focus on the signaling pathway thats include the protein kinase GCN2, the translation initiation factor eIF2α, and the transcription factor ATF4 which binds the Amino-Acid Response Element (AARE) to turn on transcription. Then, we will discuss how GCN2 function is relevant for the control of biological processes and is deregulated in several pathologies.