UCMA (upper zone of growth plate and cartilage matrix associated) is a vitamin K-dependent protein with exceptionally high γ-carboxyglutamic acid (Gla) residue content, functioning as a calcium modulator in the extracellular matrix 1. Primarily, UCMA promotes osteoblast differentiation and mineralization as a direct transcriptional target of Runx2 and Osterix, the master regulators of bone formation 2. UCMA enhances mineralized nodule formation in osteoblasts and cell adhesion, with recombinant UCMA protein demonstrating anabolic potential for treating osteoporosis 3. Mechanistically, UCMA protects cartilage through direct physical interaction with ADAMTS5 aggrecanase, blocking ADAMTS5-triggered and IL-1β-triggered aggrecanolysis while inhibiting osteophyte formation 4. The protective function is critically dependent on proper γ-carboxylation status 5. Beyond skeletal tissues, UCMA inhibits triple-negative breast cancer cell migration, invasion, and proliferation, with high expression correlating with favorable relapse-free survival 6. Clinically, UCMA represents a novel biomarker for rheumatoid arthritis, with elevated serum levels correlating with disease activity, cartilage degradation markers, and inflammatory cytokines 7. UCMA shows promise as both an anabolic therapeutic agent for bone loss and a protective factor against degenerative joint and inflammatory diseases 8.