optineurin

Optineurin is a cytosolic adaptor protein encoded by the OPTN gene in humans. It participates in vesicle trafficking within the Golgi network and acts as a selective autophagy receptor, linking ubiquitinated cargo to the autophagy machinery.

It contains multiple functional regions, including a coiled-coil domain that promotes dimerization and interactions with other proteins, a UBAN ubiquitin-binding region that binds linear polyubiquitin chains, and an LC3-interacting region (LIR) that enables recruitment of autophagosomes by binding LC3. Phosphorylation by TBK1 modulates its activity in autophagy and innate immune signaling, including NF-kB pathways.

In autophagy, optineurin recognizes ubiquitinated cargo such as damaged mitochondria or intracellular pathogens and facilitates their sequestration into autophagosomes for degradation (mitophagy and xenophagy). It also participates in Golgi maintenance and membrane trafficking, in part through interactions with Rab8 GTPase and myosin VI.

Clinical relevance: Mutations in OPTN are associated with neurodegenerative diseases, notably familial amyotrophic lateral sclerosis (ALS) and certain forms of glaucoma such as normal tension glaucoma. Loss or alteration of optineurin function is thought to impair autophagic clearance and neuronal resilience or predispose retinal ganglion cells to degeneration.

Optineurin is broadly expressed, with high levels in brain and retina, and localizes to the Golgi region and cytoplasmic organelles. Under stress conditions it can form punctate structures and participate in stress-induced autophagy.