Lysyl oxidase-like 4 (LOXL4) (LOXL4)

Lysyl oxidase-like 4 (LOXL4) is a secreted, copper-dependent amine oxidase and the most recently identified member of the lysyl oxidase (LOX) family [1, 3]. Its primary biological function involves the oxidative deamination of lysine and hydroxylysine residues in collagen and elastin, which facilitates the formation of covalent cross-links essential for the structural integrity and remodeling of the extracellular matrix (ECM) [8, 10]. Beyond its role in ECM maintenance, LOXL4 is heavily implicated in the progression of various malignancies, including head and neck squamous cell carcinoma, gastric cancer, and breast cancer, where it often promotes epithelial-mesenchymal transition (EMT), invasion, and metastasis through the activation of signaling pathways such as FAK/Src [1, 2, 12]. Interestingly, LOXL4 exhibits a context-dependent dual role, acting as a tumor suppressor in certain cancers like bladder and lung cancer while functioning as an oncogene in others [1, 3]. Therapeutically, LOXL4 is considered a promising target for both oncology and fibrotic diseases, with research focusing on small-molecule pan-LOX inhibitors like beta-aminopropionitrile (BAPN) and experimental monoclonal antibodies designed to neutralize its activity [1, 5, 12]. Clinical interest also extends to its use as a prognostic biomarker, as its expression levels and presence in exosomes correlate with disease severity and patient outcomes [1, 13, 14].

Other names

LOXCLysyl oxidase homolog 4Lysyl oxidase-like protein 4Lysyl oxidase-related protein C

Inhibition of the oxidative deamination of lysine and hydroxylysine residues in collagen and elastin, preventing covalent cross-linking and extracellular matrix stabilization [8, 10], as well as inhibiting downstream signaling pathways like FAK/Src [1, 7].