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We recently discovered that the collagen IV scaffolds of bovine, mouse, and Drosophila melanogaster tissues are stabilized by sulfilimine chemical bonds (S = N) (20⇓–22). The bond is a covalent cross-link between methionine-93 (Met93) and lysine-211 or hydroxylysine-211 (Lys211/Hyl211) residues that stabilizes the noncollagenous (NC1) interface of adjoining triple helical protomers (Fig. 1A). Peroxidasin, an animal heme peroxidase embedded in basement membrane, forms these sulfilimine cross-links by producing hypohalous acids as intermediates for Met93 oxidization (21, 22). Here, we explored whether the sulfilimine cross-link of collagen IV is a fundamental requirement in the genesis and evolution of tissues in Eumetazoa. We show the cnidarian origin and essentiality of the sulfilimine cross-link in tissue development and the cnidarian origin of the paradoxical anabolic function of hypohalous acids in tissue genesis.