TLL2 (Tolloid Like 2) is a metalloendopeptidase that functions as a protease specifically processing pro-lysyl oxidase, with critical roles in extracellular matrix organization and development 1. The gene influences dorsal-ventral patterning and skeletogenesis during embryogenesis, and notably functions as an activator of myostatin (growth differentiation factor 8), which negatively regulates skeletal muscle growth 2. TLL2 has emerged as clinically significant across multiple disease contexts. Genetic association studies identify TLL2 variants with bipolar disorder susceptibility, supported by cross-species genetics showing overlap between mouse avoidance behavior loci and human bipolar disorder linkage regions 1. In lung adenocarcinoma, elevated TLL2 expression correlates with advanced tumor stage, poor overall survival, and immune infiltration patterns, positioning it as a potential immunotherapeutic target and prognostic biomarker 3. Additionally, TLL2 mutations appear associated with frequent exacerbations in chr10 obstructive pulmonary disease and represent novel genetic modifiers in spinal muscular atrophy, where mutations can influence disease severity by affecting myostatin regulation 42. TLL2 variants also associate with pulmonary artery involvement in Takayasu arteritis and cholesterol metabolism in African populations 56.