ADAMTSL1 (ADAMTS like 1) is a secreted glycoprotein that localizes to the endoplasmic reticulum lumen and plays critical roles in tissue development and repair. The protein undergoes C-mannosylation, a post-translational modification essential for proper protein folding and secretion 12. ADAMTSL1 functions in tissue repair processes, particularly in myocardial interstitial fibrosis where it is implicated in fibroblast activation pathways 3. In skeletal development, ADAMTSL1 is strongly expressed in condensed mesenchymal cells of the mandibular condyle, where it may regulate aggrecan cleavage in condylar cartilage 4. The protein also shows motor-associated expression in peripheral nerve Schwann cells 5. Disease relevance includes mandibular prognathism, where mutations cause failure of aggrecan cleavage leading to mandibular overgrowth 4. A C-mannosylation-defective mutation (p.Trp42Arg) causes a complex phenotype including congenital glaucoma, craniofacial anomalies, and systemic features through dominant-negative effects on protein secretion 1. Genetic variants in ADAMTSL1 are also associated with breast cancer prognosis in young women 6 and affect prasugrel pharmacokinetics 7. Clinical significance lies in its potential as a therapeutic target for fibrotic diseases and genetic counseling for developmental disorders.