TARDBP encodes TAR DNA-binding protein 43 kDa (TDP-43), a multifunctional RNA-binding protein primarily localized to the nucleus. TDP-43 regulates RNA biogenesis through its two RNA recognition motifs (RRM1 and RRM2), which preferentially bind GU-rich sequences in long introns and 3' untranslated regions (3'UTRs) 1. It controls splicing of diverse RNAs including neuronal survival factors and represses nonconserved cryptic exons, maintaining intron integrity 2. TDP-43 also regulates mRNA stability by recruiting deadenylase complexes and participates in stress granule formation during oxidative stress 3. Additionally, it maintains mitochondrial homeostasis and supports muscle regeneration 4. TDP-43 dysfunction is central to multiple neurodegenerative diseases. Cytoplasmic aggregation with nuclear clearance characterizes amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), and appears in up to 57% of Alzheimer's disease cases 5. TARDBP mutations are among the most common genetic causes of ALS 6. Nuclear-to-cytoplasmic mislocalization precedes aggregation and drives pathology through both loss of normal RNA regulatory function and gain-of-function toxicity, including altered splicing, increased DNA damage, and mitochondrial dysfunction 7. TDP-43 aggregation induced by oxidative stress sequesters microRNAs and mitochondrial proteins, creating a stress-aggregation cycle 8. Understanding TDP-43 mislocalization mechanisms offers therapeutic targets for these neurodegenerative conditions.