Beta-arrestins are multifunctional proteins that regulate G-protein-coupled receptor (GPCR) desensitization, signaling, and internalization. They are involved in various neurodegenerative diseases, including Alzheimer's disease (AD), frontotemporal dementia (FTD), and Parkinson's disease (PD). Beta-arrestins interact with non-GPCR receptors and play roles in disease pathogenesis. In AD, beta-arrestins interact with gamma-secretase, increasing amyloid-beta production. In FTD, beta-arrestin oligomers inhibit autophagy, leading to tau accumulation. In PD, beta-arrestins are upregulated, and beta-2AR regulates SNCA gene expression. Beta-arrestins have distinct expression patterns and functions, with beta-arrestin1 and beta-arrestin2 showing different interactions with GPCRs. They also regulate non-GPCR signaling pathways, such as in TRPV4 and NMDAR signaling. Beta-arrestins are involved in neurogenesis and synaptic function. In neurodegenerative diseases, beta-arrestins may serve as therapeutic targets. Current therapies for these diseases focus on symptom management, but beta-arrestins offer potential for more targeted treatments. Research into beta-arrestin functions and interactions is ongoing, with implications for developing novel therapies for neurodegenerative disorders.Beta-arrestins are multifunctional proteins that regulate G-protein-coupled receptor (GPCR) desensitization, signaling, and internalization. They are involved in various neurodegenerative diseases, including Alzheimer's disease (AD), frontotemporal dementia (FTD), and Parkinson's disease (PD). Beta-arrestins interact with non-GPCR receptors and play roles in disease pathogenesis. In AD, beta-arrestins interact with gamma-secretase, increasing amyloid-beta production. In FTD, beta-arrestin oligomers inhibit autophagy, leading to tau accumulation. In PD, beta-arrestins are upregulated, and beta-2AR regulates SNCA gene expression. Beta-arrestins have distinct expression patterns and functions, with beta-arrestin1 and beta-arrestin2 showing different interactions with GPCRs. They also regulate non-GPCR signaling pathways, such as in TRPV4 and NMDAR signaling. Beta-arrestins are involved in neurogenesis and synaptic function. In neurodegenerative diseases, beta-arrestins may serve as therapeutic targets. Current therapies for these diseases focus on symptom management, but beta-arrestins offer potential for more targeted treatments. Research into beta-arrestin functions and interactions is ongoing, with implications for developing novel therapies for neurodegenerative disorders.