OPTN (optineurin) is a multifunctional autophagy receptor that plays critical roles in cellular homeostasis and neuroprotection. Its primary function involves selective autophagy, particularly mitophagy, where it recognizes and targets damaged mitochondria for degradation 1. OPTN facilitates mitochondrial transport by directly interacting with microtubules and the TRAK1/KIF5B transport complex, stabilizing them for proper anterograde axonal mitochondrial delivery 2. The protein also regulates cell fate decisions in mesenchymal stem cells by clearing FABP3 through selective autophagy, thereby maintaining bone-fat balance 3. Additionally, OPTN suppresses RIPK1-dependent inflammatory signaling and necroptosis 4. OPTN mutations are associated with amyotrophic lateral sclerosis (ALS) and normal tension glaucoma (NTG) 52. Loss of OPTN function leads to progressive neurodegeneration, including dysmyelination, axonal degeneration, and retinal ganglion cell death 42. In liver injury models, OPTN-mediated mitophagy preserves mitochondrial homeostasis and protects against drug-induced hepatotoxicity 6. The protein's neuroprotective effects depend on its C-terminus, and truncation mutations cause late-onset neurodegeneration, establishing OPTN as crucial for neuronal survival and axonal integrity.