Hsf2, or heat shock factor 2, is a crucial regulator involved in various stress-related and developmental processes. It plays a role in pathways such as the stress-responsive pathway related to Rubinstein-Taybi syndrome (RSTS), and is involved in processes like aerobic glycolysis regulation in hepatocellular carcinoma (HCC), autophagy response modulation, and spermatogenesis and corticogenesis [1,2,4,5]. Genetic models are valuable for studying its functions.

In RSTS, patient-derived primary cells show decreased Hsf2 levels due to disrupted acetylation by CBP/EP300, leading to Hsf2-dependent changes in molecular chaperones and stress response, and disturbing neuroepithelial integrity in organoid models [1]. In HCC, silencing Hsf2 expression decreased cell proliferation as it promotes cell proliferation via positive regulation of aerobic glycolysis by epigenetically silencing FBP1 [2]. In acute liver injury, hsf2bp-KO and hsf2bp-TG mouse models showed that Hsf2BP protects against injury by regulating Hsf2/HSP70/MAPK signaling [3]. In cancer, loss of either Hsf1 or Hsf2 results in a dysregulated response to nutrient stresses in vitro and reduced tumor progression in xenografts, indicating Hsf2 is a critical cofactor of Hsf1 in malignancy [6].

In conclusion, Hsf2 is essential for multiple biological functions including stress response, cell proliferation, and autophagy. Model-based research, especially through gene knockout mouse models, has revealed its significance in diseases like RSTS, HCC, acute liver injury, and cancer. Understanding Hsf2's functions provides insights into disease mechanisms and potential therapeutic targets.