Lysyl oxidase-like protein (LOXL (for the family); specific members are LOXL1, LOXL2, LOXL3, LOXL4)

Lysyl oxidase-like proteins (LOXLs) are a family of copper-dependent extracellular enzymes that catalyze the oxidative deamination of lysine or hydroxylysine residues in collagen and elastin, producing aldehyde groups necessary for the formation of covalent cross-links in connective tissue. The LOXL family comprises five members in mammals: lysyl oxidase (LOX—prototypic) and the homologs LOXL1 through LOXL4. All share a conserved C-terminal catalytic domain and require copper and lysyl tyrosylquinone as cofactors. LOXL proteins are essential for normal connective tissue development, structural integrity, and wound repair. In pathology, LOXL members—especially LOXL2—are upregulated in fibrotic diseases and promote cancer metastasis by remodeling the extracellular matrix, facilitating tumor cell migration, and potentially regulating gene expression. Inhibitors, including simtuzumab (an antibody against LOXL2), have been developed and tested in clinical trials for fibrotic diseases and cancer. Therapeutic targeting carries safety risks due to the broad physiological importance of collagen and elastin cross-linking[1][2][3][4][5][6][7].

Other names

LOXLLysyl oxidase-like 1Lysyl oxidase-like 2Lysyl oxidase-like 3Lysyl oxidase-like 4lysyl oxidase homologsLOXL1LOXL2LOXL3LOXL4

Inhibition of LOXL catalytic activity; Blockade of cross-linking formation in collagen and elastin; Interference with ECM remodeling associated with tumor invasion or fibrosis