GCN1 (General Control Nonderepressible 1), also designated as GCN1L1, is a member of the GCN1 protein family. Its core function is to serve as a central regulator of the integrated stress response (ISR), acting as a key molecular adaptor that facilitates the activation of GCN2 kinase. Under stress conditions such as amino acid starvation, GCN1 binds uncharged tRNA through its C-terminal domain while concurrently binding and activating GCN2 via its N-terminal domain. This leads to the phosphorylation of eIF2α, thereby initiating the ISR to modulate translation and gene expression. Furthermore, GCN1 participates in ribosome-associated quality control (RQC). In coordination with the RQT complex, it mediates the ubiquitination and subsequent degradation of aberrant nascent polypeptide chains on stalled ribosomes, thus preserving protein homeostasis.