ADAM21 (ADAM metallopeptidase domain 21) is a transmembrane metalloprotease that functions in multiple biological processes. ADAM21 exhibits metalloendopeptidase activity and is involved in sperm maturation and fertilization processes 1. In the nervous system, ADAM21 plays a role in neurogenesis and axonal growth, being uniquely associated with growing axons in the adult brain and functioning in regenerative processes following neuronal injury 23. The protein demonstrates significant clinical relevance in cancer progression, particularly in hepatocellular carcinoma (HCC), where ADAM21 overexpression is associated with increased cell motility, invasion, migration, and metastasis 4. Clinical studies show that ADAM21 positivity correlates with vascular invasion, larger tumor size, higher histological grade, and serves as an independent prognostic marker for both overall and recurrence-free survival in HCC patients 4. Additionally, ADAM21 has been identified as a recurrent target gene for hepatitis B virus integration in liver cancer genomes and shows genetic variation in cancer stem cells of colorectal cancer 56. These findings suggest ADAM21 functions in both normal physiological processes and pathological conditions, making it a potential therapeutic target.