Gcn1 is a highly conserved protein across eukaryotes. As an upstream activator of protein kinase GCN2, it is pivotal in integrated stress responses like amino acid starvation and oxidative stress [1]. Gcn1 also acts as a ribosome collision sensor, contributing to the translation quality control pathway [1].

Gcn1 mutant mice lacking the GCN2 - binding domain suffer from growth retardation and postnatal lethality via GCN2 - independent mechanisms, while Gcn1 - null mice die early in embryonic development [3]. Inducible systemic Gcn1 deletion in adult mice using tamoxifen - inducible conditional knockout (CKO) mice led to transient body weight loss, along with decreases in liver weight, hepatic glycogen and lipid contents, blood glucose, non - esterified fatty acids, and visceral white adipose tissue weight [3]. This shows GCN1's involvement in hepatic lipid metabolism [3]. In prostate cancer, GCN1 is overexpressed and interacts with MIRO2. Targeting the MIRO2 - GCN1 axis may be a strategy to halt prostate cancer growth as MIRO2 is necessary for efficient GCN1 - mediated GCN2 kinase signaling [2].

In conclusion, Gcn1 is essential for stress responses and translation quality control. Studies using KO/CKO mouse models have revealed its role in growth, development, and metabolism - related processes, as well as in prostate cancer. Understanding Gcn1's functions provides insights into disease mechanisms and potential therapeutic targets.