COPS8, also known as COP9 Constitutive Photomorphogenic Homolog Subunit 8, is a subunit of the COP9 signalosome (CSN). The CSN functions as the cullin deneddylase, regulating the catalytic dynamics of cullin RING ligases (CRLs), which are crucial in the ubiquitin-proteasome system [2]. COPS8 is involved in multiple biological pathways, including redox and vesicle trafficking pathways, and has been linked to various disease conditions [2]. Gene knockout and conditional knockout mouse models have been instrumental in understanding its functions.

In a gut epithelium-specific COPS8 knockout mouse model, COPS8 was shown to act downstream of the AhR pathway. Exosome-like nanoparticles from mulberry bark protect against colitis in mice by inducing COPS8, which in turn leads to the production of anti-microbial peptides [1]. In cardiac-specific Cops8-CKO mice, there is impairment of autophagosome maturation, massive cardiomyocyte necrosis, and activation of the necroptotic pathway, suggesting COPS8's role in maintaining cardiomyocyte integrity [2,3].

In conclusion, COPS8 is essential for maintaining normal physiological functions in multiple tissues. Its role in the AhR pathway in gut protection against colitis and in suppressing the necroptotic pathway in cardiomyocytes, as revealed by KO/CKO mouse models, highlights its significance in gut-related inflammatory diseases and cardiac pathologies. These findings provide potential therapeutic targets for these disease areas.