Age-related macular degeneration (AMD) is a neurodegenerative blinding disease affecting the elderly. The lack of treatments able to improve vision or reverse vision loss in these patients is in part due to its multi-factorial nature, in which there is no clear causative culprit. Many of the treatments under consideration aim to target genes reported as risk factors, with marginal success, pointing to a need to think outside the box and identify other regulators of cellular homeostasis altered during aging and disease development. Here we discuss the known functions of an orphan nuclear receptor called estrogen-related receptor alpha (ESRRA) in neurodegenerative diseases that share common pathogenic pathways with AMD and discuss its potential role in AMD development and as a drug target.