Lipocalin-2 (LCN2/NGAL) is a multifunctional secretory glycoprotein that plays a critical role in the pathogenesis of ophthalmic diseases by regulating iron metabolism, inflammatory responses, and cell death pathways (ferroptosis, apoptosis). Under physiological conditions, LCN2 is expressed at low levels in tissues such as the corneal epithelium and retinal ganglion cell layer. However, its expression is significantly upregulated under pathological conditions, exhibiting highly context-dependent functionality. In major ophthalmic diseases—including dry eye disease, corneal disorders, uveitis, glaucoma, and retinal diseases—LCN2 can act either as a pro-inflammatory and pro-apoptotic pathogenic factor or as an anti-inflammatory protective agent. Targeted modulation of LCN2 expression or its downstream pathways may offer novel therapeutic strategies for ocular diseases.