TDP-43 (TAR DNA-Binding Protein 43)

Category: biomarker

An RNA-binding protein whose cytoplasmic aggregation is the hallmark pathology of ~97% of ALS cases and ~45% of frontotemporal dementia cases.

Mechanism Detail

TDP-43 normally resides in the nucleus, regulating RNA splicing, transport, and stability. In ALS, it mislocalizes to the cytoplasm, forming phosphorylated, ubiquitinated aggregates. Loss of nuclear TDP-43 function disrupts RNA processing of thousands of genes. Cryptic exon inclusion (e.g., in STMN2) is a key downstream pathogenic mechanism.

Clinical Status

STMN2 restoration therapies in development. Anti-TDP-43 antibodies and ASOs targeting TARDBP in preclinical stages. TDP-43 biomarker assays emerging for diagnosis and clinical trial stratification.

Relevant Diseases

• ALS

Relevant Therapies

• Gene Therapy

Related Terms

• SOD1
• STMN2
• RNA splicing
• Protein aggregation