The Lysosomal-Associated Protein Transmembrane Family and Neurological Disorders: Therapeutic Potential and Future Research Directions.
Lysosomal-associated protein transmembrane (LAPTM) family members-including LAPTM4A, LAPTM4B, and LAPTM5-are key regulators of lysosomal integrity, autophagy-lysosome flux, lipid metabolism, and immune responses. Dysregulation of LAPTM proteins contributes to neurological disorders such as Alzheimer's disease, Parkinson's disease, ischemic stroke, and gliomas, affecting neuronal survival, glial homeostasis, neuroinflammation, and tumor progression. In this review, we summarize recent insights into the structural features and molecular mechanisms of LAPTM proteins in the nervous system and highlight their therapeutic potential in promoting protein aggregate clearance, mitigating oxidative stress, regulating microglial polarization, and enhancing tumor immunotherapy. Future research integrating gene therapy, small-molecule modulators, multi-omics profiling, and advanced delivery platforms may enable translation of LAPTM-targeted interventions into clinical practice, offering new avenues for diagnosis, prognosis, and treatment of neurological diseases.