Ei24, also known as Etoposide-induced protein 2.4 or PIG8 (p53-induced gene 8), is an endoplasmic reticulum (ER) transmembrane protein. It plays crucial roles in multiple biological processes. It is involved in the unfolded protein response (UPR) and calcium signaling pathways during ER stress, and is also associated with autophagy, cell proliferation, and fibrosis-related pathways [1,2,3,6]. Genetic models are valuable for studying its functions.

In gene knockout studies, EI24 knockout causes failure of ER stress adaptation and apoptosis, indicating its role as an anti-apoptotic factor in ER stress signaling [1]. In pancreatic β cells, specific ablation of EI24 inhibits the autophagy process, showing its importance in autophagy flux [2]. In a renal interstitial fibrosis model, overexpression of EI24 alleviates the progression of fibrosis by inhibiting epithelial-mesenchymal transition and fibroblast activation [3]. In esophageal squamous cell carcinoma, forced overexpression of EI24 represses cell growth and sensitizes cells to chemotherapeutic agents [4]. In pancreatic tumor cells, knockdown of EI24 using siRNA or the CRISPR-Cas9 system inhibits cell proliferation, suggesting its role as a tumor promoter in this context [5]. In a pulmonary fibrosis model, overexpression of EI24 delays the progression of fibrosis by promoting autophagy [6]. In pancreatic cancer, overexpression of EI24 suppresses cancer cell growth and prompts cell cycle arrest by regulating c-Myc [7].

In conclusion, Ei24 is essential for cell adaptation to ER stress, autophagy regulation, and has implications in fibrosis and cancer development. Gene knockout and overexpression models in mice and cell lines have been instrumental in revealing its functions in these disease-related biological processes, providing potential therapeutic targets for diseases such as fibrosis and cancer.