MMP21 (matrix metallopeptidase 21) is a proteolytic enzyme with specialized functions in embryonic development and disease pathology. Primarily, MMP21 establishes left-right asymmetry during vertebrate embryogenesis 1; mutations in MMP21 cause heterotaxy, a condition characterized by reversed or randomized organ positioning and congenital heart defects 12. MMP21 may negatively regulate NOTCH-signaling and cleaves alpha-1-antitrypsin 3. The mechanism involves extracellular matrix remodeling essential for laterality establishment 1. Both biallelic recessive mutations and de novo heterozygous disruptive variants associate with heterotaxy, suggesting loss-of-function pathogenesis 34. Beyond developmental roles, MMP21 dysregulation contributes to cancer pathology. In colorectal cancer, the NF-κB-MMP21 axis promotes transformed cell invasion by reversing normal cell competition-mediated extrusion, enabling basal infiltration and carcinoma development 5. In gastric cancer, MMP21 overexpression correlates with tumor invasion, metastasis, lymph node involvement, and poor overall survival, establishing MMP21 as an independent prognostic marker 6. Thus, MMP21 functions critically in embryonic left-right patterning and aberrantly promotes epithelial-to-mesenchymal transitions in malignancy.