LOX（赖氨酰氧化酶）是一种关键的酶，负责催化胶原蛋白和弹性蛋白中赖氨酸残基的氧化脱氨反应，形成醛基并促进这些蛋白的交联，从而维持细胞外基质（ECM）的结构稳定性和机械强度。它在组织修复、纤维化、血管重塑和胚胎发育等生理过程中发挥重要作用。LOX主要在成纤维细胞、平滑肌细胞和某些肿瘤细胞中表达，其活性依赖于铜离子和维生素B6作为辅因子。LOX基因突变可能导致结缔组织疾病，如皮肤松弛症或心血管异常，因为胶原和弹性纤维的交联受损会削弱组织的完整性。LOX的过表达与纤维化疾病（如肺纤维化、肝纤维化）和肿瘤转移密切相关，因为它能增强ECM的硬化，促进肿瘤细胞的侵袭和迁移。相反，LOX表达降低可能导致伤口愈合延迟、主动脉瘤或骨质疏松，因为ECM的稳定性下降。LOX属于赖氨酰氧化酶家族（LOX家族），该家族还包括LOXL1、LOXL2、LOXL3和LOXL4。这些成员共享保守的铜结合位点和酶活性结构域，均参与ECM修饰，但各自在组织分布和功能上存在差异。例如，LOXL2在胚胎发育和肿瘤转移中作用突出，而LOXL1与弹性纤维的组装有关。LOX家族基因的异常表达常与纤维化、癌症和心血管疾病相关，因此成为潜在的治疗靶点。

Lysyl oxidase (LOX) is a copper-dependent extracellular enzyme that plays a pivotal role in the post-translational modification of the extracellular matrix (ECM) by catalyzing the oxidative deamination of lysine residues in collagen and elastin fibers. This enzymatic reaction generates reactive aldehydes that subsequently undergo spontaneous condensation to form stable covalent cross-links, thereby conferring essential tensile strength, structural integrity, and mechanical stability to connective tissues. As a founding member of the lysyl oxidase family, which also includes LOXL1, LOXL2, LOXL3, and LOXL4, LOX shares a conserved copper-binding domain and catalytic mechanism, yet exhibits distinct tissue-specific expression patterns and functional nuances compared to its isoforms, such as LOXL1’s specific involvement in elastin assembly. LOX is primarily expressed in fibroblasts, vascular smooth muscle cells, and certain tumor cells, where its activity is strictly dependent on copper ions and pyridoxal 5'-phosphate (vitamin B6) as cofactors. Physiologically, LOX is indispensable for embryonic development, tissue repair, vascular remodeling, and the maintenance of connective tissue homeostasis; consequently, loss-of-function mutations can lead to severe congenital connective tissue disorders, including cutis laxa, cardiovascular anomalies, aortic aneurysms, and osteoporosis, due to defective matrix cross-linking and compromised tissue integrity. Conversely, dysregulated overexpression of LOX is frequently observed in pathological conditions such as pulmonary and hepatic fibrosis, where it contributes to excessive ECM stiffening, and in various cancers, where it facilitates tumor cell invasion, migration, and metastasis by remodeling the microenvironment. Given its central role in regulating ECM dynamics and its strong association with fibrosis, cardiovascular disease, and malignancy, LOX and its family members have emerged as significant therapeutic targets for modulating pathological tissue remodeling and cancer progression.

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