LOXL2 is a lysyl oxidase family enzyme with dual intracellular and extracellular functions critical for tissue homeostasis and disease progression. Intracellularly, LOXL2 functions as an epigenetic regulator by catalyzing H3K36ac deacetylation, which represses oncogenic gene expression including c-MYC, CCND1, HIF1A, and CD44 1. Loss of nuclear LOXL2 leads to aberrant H3K36 acetylation and oncogenic pathway activation, contributing to uterine hypertrophy and carcinoma development 1. Extracellularly, LOXL2 promotes collagen cross-linking in the extracellular matrix, facilitating tissue remodeling processes 2. In cancer contexts, LOXL2 exhibits paradoxical roles: while nuclear LOXL2 acts as a tumor suppressor, secreted LOXL2 promotes metastasis through ECM remodeling and macrophage-mediated signaling 3. LOXL2 also functions as an endogenous ligand for PEAR1, inducing Ser891 phosphorylation that stabilizes CD44 and enhances triple-negative breast cancer metastasis 4. Additionally, skeletal muscle-derived LOXL2 acts as a myokine that contributes to pulmonary vascular remodeling in heart failure with preserved ejection fraction through CNPY2-p53 signaling 5. In liver fibrosis, LOXL2 promotes collagen deposition and can be therapeutically targeted 6. LOXL2 also enhances chemotherapy resistance in glioblastoma through blood-tumor barrier modifications 7.