ADAM17, also known as tumor necrosis factor-α converting enzyme (TACE), is a cell membrane-bound protease of the ADAM family. It is involved in "ectodomain shedding" of numerous substrates like cytokines, growth factors, adhesion proteins and their receptors, thus regulating intracellular signaling and membrane protein degradation [6,7]. ADAM17-mediated processes participate in various biological pathways, with significant implications for health and disease [1,2,5,6,7,8]. Genetic models, such as KO/CKO mouse models, have been crucial in understanding its functions.

In atherosclerosis, ADAM17 promotes vascular inflammation in endothelial cells, smooth muscle cells, and macrophages, regulating the disease's development [1]. In the context of tumors, it has immunomodulatory roles, with over 90 substrates regulated, some relevant to tumor formation [2]. In colorectal cancer, tumor-derived exosomal ADAM17 enhances vascular permeability, promoting pre-metastatic niche formation and metastasis, and ADAM17 selective inhibitors can reduce metastasis in vivo [3]. In liver damage, ADAM17 has a central role as its substrates are involved in processes like apoptosis, necroptosis, liver regeneration, and hepatocyte protection [5]. In hair loss, a dominant ADAM17 variant leads to hair follicle stem cell exhaustion and alopecia through enhanced ubiquitination and degradation of ADAM17 protein, affecting the Notch signaling pathway [4].

In conclusion, ADAM17 is a key protease involved in multiple biological functions, mainly through substrate shedding. Model-based research, especially KO/CKO mouse models, has revealed its significant roles in diseases such as atherosclerosis, tumors, liver damage, and hair loss-related conditions. Understanding ADAM17's functions provides potential targets for treating these diseases.