Optineurin (OPTN) is a novel protein discovered by yeast two-hybrid screening. It has been linked to neurodegenerative illnesses such as glaucoma and amyotrophic lateral sclerosis (ALS) via its involvement in numerous signaling pathways. Research shows that this protein regulates the NF-κB, TBK1, and interferon signaling pathways, contributing to the body’s innate immune response. In this review, we consolidate recent research findings, define the role of OPTN in the innate immune response, outline its regulatory interactions with major innate immunity components, and address OPTN’s possible involvement in illness via innate immune processes.