Atox1, also known as Antioxidant 1 or antioxidant protein 1, is a copper chaperone that plays a crucial role in regulating intracellular copper ion balance [1,2,3,4,5,6,7,8,9]. It transfers copper to the copper export P-type ATPases ATP7A and ATP7B for copper excretion, and is involved in various pathways related to neurotransmitter biosynthesis, iron efflux, neovascularization, wound healing, and blood pressure regulation [7]. It also has antioxidant properties and may act as a transcription factor regulating Ccnd1 [4]. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable for studying Atox1's functions.

In a mouse model of TNBS-induced colitis, Atox1 knockout preempted the up-regulation of inflammatory cytokines, M1 polarization markers, and p47phox expression induced by TNBS, indicating Atox1 plays a pro-inflammatory role in intestinal inflammation via the ROS-NLRP3 inflammasome pathway [3]. In a traumatic brain injury (TBI) mouse model, Atox1 expression decreased after TBI. Overexpression of Atox1 in mice preserved the hippocampal structure, reduced oxidative stress, and ameliorated learning and memory impairments. In HT-22 cells with stretch injury, Atox1 overexpression mitigated oxidative stress. Knockdown of DJ-1 in HT-22 cells impaired Atox1's antioxidant capacity, suggesting DJ-1 mediates Atox1's ability to withstand oxidative stress [1].

In conclusion, Atox1 is essential for copper homeostasis and has antioxidant functions. KO/CKO mouse models have revealed its roles in intestinal inflammation and TBI. Understanding Atox1's functions through these models provides insights into potential therapeutic approaches for post-traumatic neurological dysfunction and inflammatory bowel disease [1,3].