STMN2 is a microtubule-regulating protein essential for axonal growth and regeneration in motor neurons. It functions as a stabilizer of microtubule dynamics, with its expression critically dependent on proper nuclear function of the RNA-binding protein TDP-43 1. Mechanistically, TDP-43 binds to GU-rich regulatory regions within STMN2 pre-mRNA to prevent cryptic splicing and premature polyadenylation 2. When TDP-43 is depleted or mislocalized—a hallmark of neurodegeneration—cryptic splice sites become exposed, producing truncated, non-functional STMN2 mRNA 3. This truncation leads to rapid protein depletion, particularly during cellular stress 4. STMN2 loss is functionally linked to impaired axonal regeneration and neurite outgrowth in motor neurons 1. Notably, restoring STMN2 expression rescues regenerative capacity even when TDP-43 is depleted 3. Additionally, STMN2 mRNA localization along neurites promotes local protein synthesis and enhances neurite outgrowth 5. Clinically, STMN2 dysfunction is a disease hallmark in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease 6, 7. Truncated STMN2 serves as a molecular marker of TDP-43 pathology 8, while therapeutic strategies targeting STMN2 restoration through antisense oligonucleotides show promise for correcting pre-mRNA misprocessing 2.