TLL1 (Tolloid-like 1) encodes a metalloproteinase that plays critical roles in embryonic development and extracellular matrix processing. The protein functions as a protease that processes procollagen C-propeptides and cleaves substrates including chordin, pro-biglycan, and pro-lysyl oxidase 1. TLL1 is essential for dorsal-ventral patterning and skeletogenesis during development, with knockout studies demonstrating that simultaneous ablation of Bmp1 and Tll1 in mice produces osteogenesis imperfecta characterized by brittle bones, spontaneous fractures, and defective osteocyte maturation 1. The gene is also required for proper cardiac development, as mice lacking TLL1 exhibit incomplete atrial septal closure leading to mid-gestational lethality 2. Human genetic studies have linked TLL1 disruption to atrial septal defects, with chr4 rearrangements affecting the TLL1 locus associated with congenital heart defects 3. Beyond developmental roles, recent research indicates TLL1 involvement in cancer progression, where it promotes prostate cancer metastasis through TGF-β pathway activation and affects immune cell infiltration 4. Polymorphisms in TLL1 have been investigated for associations with various diseases including hepatocellular carcinoma and coronary heart disease, though results vary across populations 56.