Purpose of Review <p>This review aims to highlight the critical role of acid-sensing ion channels (ASICs) in the neurodegenerative pathway, providing an overview of recent research and exploring their potential as therapeutic targets for neurodegenerative diseases.</p> Recent Findings <p>Recent research has revealed that ASICs are significantly involved in various stages of neurodegeneration. In Alzheimer's disease, ASICs mediate amyloid beta accumulations, neuroinflammation, synaptic plasticity alterations, and neuronal excitability. Similarly, in Parkinson's disease, ASICs are implicated in dopaminergic neuronal loss and contribute to the effects of gene mutations and mitochondrial dysfunction. In Amyotrophic Lateral Sclerosis, ASICs are linked to excitotoxicity, genetic mutations, and acidosis. Furthermore, ASICs are associated with acidotoxicity and acidosis in Huntington's disease, and they play a dual role in stroke, contributing to cell damage after brain ischemia while also offering neuroprotection. Additionally, ASICs have been found to influence both neuroinflammation and neuroprotection in multiple sclerosis.</p> Summary <p>ASICs are emerging as crucial players in the pathomechanisms of various neurodegenerative diseases, demonstrating their potential as therapeutic targets. By emphasizing the role of ASICs in the neurodegenerative pathway, this review seeks to inform and guide future research towards the development of innovative therapeutic approaches aimed at mitigating the progression of these debilitating conditions.</p>