Stau1, also known as Staufen double-stranded RNA binding protein 1, is a multifunctional double-stranded RNA-binding protein. It plays a crucial role in mediating RNA metabolism, which is involved in various physiological and pathological events [1,2,3,4,5,6,7,8,9]. It participates in pathways such as mTOR signaling, autophagy, adipocyte differentiation, amyloidogenesis, tau phosphorylation, and ferroptosis regulation, highlighting its overall biological importance. Genetic models, especially KO/CKO mouse models, are valuable tools to study its functions.

In neurodegenerative disease models, reducing Stau1 levels in mice with ALS mutations normalizes mTOR activity and autophagy-related marker proteins. For example, in mouse models of Huntington's disease, endogenous Stau1 forms cytoplasmic condensate that recruits MTOR mRNA at its 5'UTR and promotes its translation, leading to mTOR hyperactivation and autophagy-lysosome dysfunction. Interference of Stau1 condensate can ameliorate these conditions [1,4,7]. In addition, in APP/PS1 mice (an Alzheimer's disease model), Stau1 knockdown decreases the protein levels of β-amyloid converting enzyme 1 (BACE1) and Aβ [3].

In conclusion, Stau1 is essential in multiple biological processes mainly through its role in RNA metabolism. Studies using KO/CKO mouse models have significantly contributed to understanding its role in neurodegenerative diseases, such as Alzheimer's and ALS, providing potential therapeutic targets for these diseases.