AREL1, also known as apoptosis-resistant E3 ubiquitin protein ligase 1, is a HECT-type E3 ubiquitin ligase. It plays a crucial role in regulating apoptosis, necroptosis, and inflammation. AREL1 is involved in pathways related to cell survival and death, and its activity is important for maintaining normal cellular homeostasis. Genetic models, such as gene knockout models, can be valuable for studying its functions in vivo [2,4,5].

In vascular endothelial cells, AREL1 is downregulated by TGF-β and miR-320b. Overexpression of AREL1 inhibits TGF-β-induced apoptosis by downregulating SMAC, which is a pro-apoptotic protein [1]. In TNF-induced necroptosis, AREL1 ubiquitinates MTX2, leading to its degradation and inhibiting necroptosis. The inhibition of AREL1-dependent ubiquitination of MTX2 may sensitize tumor cells to TNF-induced necroptosis [2]. In macrophages, AREL1, along with UBE2L3 and TRIP12, limits inflammation by promoting the turnover of pro-IL-1β [3].

In conclusion, AREL1 is a key regulator in apoptosis, necroptosis, and inflammation processes. Its study through gene knockout or other genetic models provides insights into its role in diseases such as arteriosclerosis, where abnormal apoptosis of vascular endothelial cells is a feature, and potentially in tumor cell sensitivity to necroptosis-inducing agents [1,2].