ADAM10, a member of the A Disintegrin And Metalloproteinase (ADAM) superfamily, is a membrane-bound protein with its catalytic domain on the cell surface. It functions as a sheddase, cleaving over 100 anchored cell-surface proteins, and is involved in crucial pathways such as Notch signaling [2,3,6]. ADAM10 is expressed in most tissues and plays important roles in mammalian development, physiology, and is also the primary α-secretase in the non-amyloidogenic cleavage of APP [3,5].

In the context of diseases, ADAM10 has been studied in various models. In hair follicles, ablation of the ADAM10-Notch signaling axis in mice led to skin dysbiosis, innate lymphoid cell-mediated hair follicle destruction, and irreversible alopecia, indicating its role in maintaining skin microbiota and protecting hair follicles from inflammation [6]. In renal diseases, ADAM10 is closely associated with the progress of glomerular diseases, acute kidney injury, and renal fibrosis, and may be a potential therapeutic target [1]. In cancer, ADAM10 cleavage of Trop-2 acts as an activator switch for cancer growth and metastasis, and it also modulates the efficacy of T-cell-mediated therapy in solid tumors [7,8]. In sepsis, ADAM10 acts as a "molecular scissor" regulating the inflammatory response by cleaving various membrane-protein substrates, though its substrate-specific modulation in sepsis is yet to be fully elucidated [4]. In Alzheimer's disease, ADAM10 levels are altered in platelets, plasma, serum, and CSF, potentially making it a complementary biomarker, but more studies are needed to establish cut-off values [9].

In conclusion, ADAM10 is a multifunctional protein involved in diverse biological processes. Studies using gene-knockout or conditional-knockout mouse models have revealed its significance in multiple disease areas, including skin disorders, renal diseases, cancer, sepsis, and Alzheimer's disease. These findings highlight the potential of ADAM10 as a therapeutic target and biomarker in these diseases.