TERF2, also known as Telomeric Repeat-binding Factor 2, is a crucial component of the telomere-binding protein complex. It plays a vital role in maintaining telomere stability. Telomeres are essential for chromosome stability, and TERF2 is involved in several pathways, with its functions being fundamental in both physiological and pathological cell fate determination [2,3]. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, can be used to study its functions in vivo.

In esophageal carcinoma, TERF2 is overexpressed and contributes to cell proliferation, potentially via the DDR/TP53 signaling pathway [2]. Silencing TERF2 in cells promotes the cytosolic translocation and autophagic activity of HMGB1, uncovering a new role of TERF2 in regulating autophagy [1]. In post-hypoxic brain damages, downregulating Terf2 in hippocampal neural cells of unchallenged mice triggers an excitotoxicity-like phenotype, while overexpressing it in mice subjected to post-hypoxic treatment prevents brain damages [4].

In conclusion, TERF2 is key for telomere stability and has functions in processes like autophagy, cell proliferation, and post-hypoxic stress response. The study of TERF2 using KO/CKO mouse models contributes to understanding its roles in diseases such as esophageal carcinoma and neurodegenerative diseases related to post-hypoxic stress.