Investigating the Molecular Mechanisms of RNA Binding Protein ARPP21 in Amyotrophic Lateral Sclerosis

In ALS, a protein called ARPP21 forms tiny, pulsating clumps inside neurons that may be disrupting the brain's ability to make essential proteins. ALS destroys the motor neurons that control movement, leading to paralysis and death, usually within a few years. Scientists recently discovered that mutations in the gene for ARPP21 are linked to the disease. This protein normally regulates protein translation—the process cells use to build proteins from genetic instructions—and does so in a unique, rhythmic way that no other known RNA-binding protein shares. When ARPP21 is mutated, these pulsatile granules become dysfunctional, and protein production likely drops. This project will uncover exactly how ARPP21 controls translation, why it forms these granules, and how mutations derail both processes. This is fundamental science. There is no immediate treatment or diagnostic tool here. But understanding the molecular machinery that breaks down in ALS is a necessary step toward designing therapies that could one day restore normal protein production in neurons. Similar fundamental work on RNA-binding proteins has already opened new avenues for treating other neurodegenerative diseases.