Neuron-derived clone 77 (Nur77), a member of the orphan nuclear receptor family, is expressed and activated rapidly in response to diverse physiological and pathological stimuli. It exerts complex biological functions, including roles in the nervous system, genome integrity, cell differentiation, homeostasis, oxidative stress, autophagy, aging, and infection. Recent studies suggest that Nur77 agonists alleviate symptoms of neurodegenerative diseases, highlighting its potential as a therapeutic target in such conditions. In cancer, Nur77 demonstrates dual roles, acting as both a tumor suppressor and promoter, depending on the cancer type and stage, making it a controversial yet promising anticancer target. This review provides a structured analysis of the functions of Nur77, focusing on its physiological and pathological roles, therapeutic potential, and existing controversies. Emphasis is placed on its emerging applications in neurodegenerative diseases and cancer, offering key insights for future research and clinical translation.