Lysyl oxidases play a central role in extracellular matrix remodelling during development and tumour growth and fibrosis, through cross-linking of collagens and elastin. We have limited knowledge of the structure and substrate specificity of these secreted enzymes. Lysyl oxidases share a conserved C-terminal catalytic domain but differ in their N-terminal region, which is composed of four repeats of scavenger receptor cysteine-rich (SRCR) domains in LOXL2. We investigated by X-ray scattering and electron microscopy the low-resolution structure of the full-length enzyme and of a shorter form lacking the catalytic domain. Our data demonstrate that LOXL2 has a rod-like structure with a stalk composed of the SRCR domains and the catalytic domain at its tip. We detected direct interaction between LOXL2 and tropoelastin and also LOXL2-mediated deamination of tropoelastin. Using proteomics, we identified several allysines together with cross-linked tropoelastin peptides. The elastin-like material generated was resistant to trypsin proteolysis and displayed mechanical properties similar to mature elastin. Finally, we detected the codistribution of LOXL2 and elastin in the vascular wall. Altogether, these data suggest that LOXL2 could participate in elastogenesis in vivo and could be used as a means of cross linking tropoelastin in vitro for biomimetic and cell compatible tissue engineering purposes.