ADAMTS18 is a secreted zinc-dependent metalloproteinase that plays crucial roles in development, tissue homeostasis, and disease processes 1. The protein functions as an extracellular matrix remodeling enzyme with metalloendopeptidase activity, essential for morphology and organogenesis of epithelial organs including lung, kidney, breast, salivary glands, and lacrimal glands, as well as vascular and neuronal systems 1. ADAMTS18 serves as a novel activator of latent TGF-β through its KPFR sequence, which disrupts the latency-associated peptide interaction with TGF-β, releasing mature TGF-β1 2. In disease contexts, ADAMTS18 frequently undergoes promoter hypermethylation in various cancers, leading to reduced expression and tumor progression 345. Functionally, ADAMTS18 acts as a tumor suppressor by inhibiting cell proliferation, migration, and invasion while promoting apoptosis 5. The gene also contributes to bone mineral density regulation and hip fracture risk across different ethnic groups 6. Additionally, ADAMTS18 deficiency disrupts brain methylation metabolism, neuroinflammatory responses, and blood-brain barrier integrity, affecting microglial function and CNS homeostasis 7. These findings highlight ADAMTS18's multifaceted role in development, cancer suppression, and neurological function.