Study reveals "substrate selection failure" in UFM1 modification causes lethal neurodevelopmental disease

A research group at Juntendo University identified that mutations in CDK5RAP3, a key factor in UFM1 modification, cause lethal neurodevelopmental disorders. Unlike previous theories focusing on enzyme deficiency, this study highlights "substrate selection failure" as the primary cause. This leads to the collapse of endoplasmic reticulum ribosome quality control (ER-RQC). The team also demonstrated that antisense oligonucleotides can potentially treat these molecular abnormalities by correcting splicing errors, offering a new path for personalized medicine.