Many studies in the open literature have highlighted the critical roles of endoplasmic reticulum stress and ferroptosis in neurological diseases such as neurodegenerative diseases, brain injuries, and depression, indicating that they are involved in the onset and progression of these diseases. Therefore, it is essential to explore the regulatory mechanisms and potential interventions targeting endoplasmic reticulum stress and ferroptosis in neurological diseases. However, most existing research has primarily focused on the unidirectional mechanisms of endoplasmic reticulum stress and ferroptosis within the nervous system, with a lack of in-depth investigations into their interactions. In this paper, we first present an overview of the pathogenesis of endoplasmic reticulum stress and ferroptosis, along with their roles in neurological diseases. We then summarize the latest findings on the interaction mechanism between endoplasmic reticulum stress and ferroptosis from the perspectives of calcium iron homeostasis, reactive oxygen species, microenvironment, and related factors. Finally, we explore the potential molecular mechanisms and targeted interventions associated with endoplasmic reticulum stress and ferroptosis in neurological diseases.

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http://dx.doi.org/10.1007/s11064-025-04348-4DOI Listing

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