ataxin2

Ataxin-2 is a cytoplasmic RNA-binding protein encoded by the human ATXN2 gene. It is conserved across vertebrates and participates in RNA metabolism, translation regulation, and the assembly and function of stress granules, which form in response to cellular stress. The protein contains motifs that enable interactions with other RNA-binding proteins, including a PAM2 motif that binds poly(A)-binding protein, linking ATXN2 to mRNA processing and translational control.

Normal ATXN2 function is involved in fine-tuning mRNA translation and turnover and in cellular stress responses. Through its interactions within messenger ribonucleoprotein complexes, it contributes to the proper regulation of gene expression in neurons and other cell types. Disruptions to ATXN2 function, including altered expression levels, can affect RNA metabolism and protein homeostasis.

Genetic disease associated with ATXN2 is spinocerebellar ataxia type 2 (SCA2), an autosomal dominant neurodegenerative disorder. SCA2 results from an expansion of the CAG trinucleotide repeat in ATXN2, which encodes a polyglutamine tract in the protein. Normal alleles typically contain a small number of repeats, while pathogenic expansions (commonly more than about 34 repeats) cause progressive cerebellar ataxia, dysarthria, and other motor symptoms. Intermediate repeats (roughly 27–33) have been linked to increased risk for amyotrophic lateral sclerosis (ALS) and may influence disease features in SCA2.

Research uses cellular and animal models to study ATXN2 function and its role in neurodegeneration. Genetic testing can diagnose SCA2 and assess repeat length, aiding diagnostic clarification and genetic counseling. Therapeutic approaches under investigation include strategies to reduce mutant ATXN2 expression or modulate its RNA-protein interactions.