TEX264, or testes expressed gene 264, is a single-pass transmembrane protein. It functions as a receptor in autophagic degradation of the endoplasmic reticulum (ER-phagy) and is involved in the autophagy pathway [1,2,3,5]. Additionally, it has been linked to DNA repair processes [2,4,7,8]. Understanding TEX264 is crucial as it bridges two important cellular functions, autophagy and DNA repair, which are vital for cell survival and maintaining cellular homeostasis. Genetic models, such as KO mouse models, can significantly aid in studying its functions.

Deletion of TEX264 profoundly blocks ER-phagy, and when combined with deletion of FAM134B and CCPG1, ER-phagy is almost completely blocked, suggesting it is a major ER-phagy receptor [1]. In the context of DNA repair, TEX264 acts as a sensor for topoisomerase 1 cleavage complexes (TOP1cc) at DNA replication forks. It triggers TOP1cc processing by the p97 ATPase and mediates their delivery to lysosomes, promoting DNA damage repair and cell survival [4]. In HeLa cells, siRNA-mediated knockdown of TEX264 did not affect cell proliferation but significantly inhibited cell migration, potentially through reduced SNX27-mediated Itgα5 receptor membrane recycling [6].

In conclusion, TEX264 plays essential roles in ER-phagy and DNA repair. Model-based research, especially KO experiments, has revealed its significance in maintaining cellular functions related to these processes. In diseases like colorectal cancer, its role in DNA repair via selective autophagy of DNA lesions has clinical relevance, providing insights into potential therapeutic strategies targeting these cellular mechanisms [4].