Optineurin (OPTN)

Optineurin is a ubiquitously expressed, highly conserved 577-amino acid cytosolic protein encoded by the OPTN gene on human chromosome 10, comprising several key functional domains, including a coiled-coil region, leucine zipper, ubiquitin-binding (UBAN) domain, LC3-interacting region (LIR), and a zinc finger motif[1][2][3][4]. It acts as a selective autophagy receptor crucial for mediating degradation of ubiquitinated cellular cargo via autophagosomes, and uniquely recruits the ULK1 complex and stabilizes early phagophore formation[1][4]. Optineurin also regulates NF-κB activation and apoptosis, interacting with key partners such as TBK1, Rab8, myosin VI, and transferrin receptor, and serves as a signaling adaptor in cellular immunity and inflammation[2][5][6][7]. Dysfunction or mutation of optineurin is implicated in neurodegenerative disease (notably ALS), glaucoma, Paget’s disease, and other disorders linked to impaired autophagy or immune control[2][4][6][7]. Currently, there are no marketed drugs specifically targeting optineurin, but its fundamental role in selective autophagy, immune signaling, and neuronal survival makes it a potential future therapeutic target, with disease-causing mutations serving as biomarkers.

Other names

FIP-214.7K-interacting proteinOptic neuropathy inducing protein

Drugs or small molecules targeting optineurin would typically act by modulating selective autophagy pathways, ubiquitin signaling, or NF-κB activation; known ALS therapies do not directly target OPTN[1][4][6].