Atf5, or Activating transcription factor 5, is a prosurvival transcription factor within the basic leucine zipper (bZip) family. It is involved in cellular differentiation and enables cells to adapt to stress. ATF5 is crucial in the mammalian mitochondrial unfolded protein response (UPRmt) through mitochondria-nuclear translocation, which helps maintain mitochondrial protein homeostasis during mitochondrial stress [1,4].

In various disease models, ATF5 shows diverse effects. In diabetic kidney disease (DKD), ATF5 initially has a protective effect, but in the long run, it promotes tubulointerstitial injury by regulating HSP60 and the UPRmt pathway. Inhibition of ATF5 in db/db mice improved serum creatinine, tubulointerstitial fibrosis, and apoptosis [1]. In cardiomyocyte studies, TMEM11 enhanced m7G methylation of Atf5 mRNA, increasing ATF5 expression, which suppressed cardiomyocyte proliferation [2]. In sepsis-induced liver injury, ASGR1 promoted monocyte-to-macrophage differentiation via the NF-κB/ATF5 pathway, and ASGR1-knockdown decreased ATF5 expression, alleviating liver injury [3]. In cutaneous T cell lymphoma, ATF5 overexpression promoted malignant T cell survival through the PI3K/AKT/mTOR pathway and conferred resistance to endoplasmic reticulum stress-induced apoptosis [5].

In conclusion, ATF5 is essential for maintaining mitochondrial function and cellular stress adaptation. Through gene-knockout or related models, its role in diseases such as DKD, cardiac repair, liver injury during sepsis, and cutaneous T cell lymphoma has been revealed. Understanding ATF5's functions in these disease conditions may provide potential therapeutic targets for treatment.