Tia1, also known as T cell-restricted intracellular antigen-1, is an RNA-binding protein. It plays a role in regulating stress responses, RNA metabolism, and is involved in pathways related to translational regulation. Tia1 is of great biological importance as it impacts various cellular functions and is associated with multiple disease conditions [1-10]. Genetic models, such as knockout (KO) and conditional knockout (CKO) mouse models, have been crucial in studying its functions.

In Tia1 cKO mice crossed with PS19 MAPT P301S tauopathy mice, the peripheral macrophages showed a hyper-inflammatory phenotype, while the brains had reduced inflammation and tau pathology. This indicates Tia1's role in mediating divergent inflammatory responses in microglia and macrophages [1]. In the context of tauopathy, reduction of Tia1 protected against tau-mediated neurodegeneration, and Tia1 was required for the production of tau oligomers and regulated the neuronal response to them [2]. In EAE mice, deletion of Tia1 in the CNS alleviated neuroinflammation, demyelination, axonal damage, and neuronal loss, with IL-31RA levels decreased and autophagy enhanced [3].

In conclusion, Tia1 is a key regulator in multiple biological processes. Model-based research, especially using KO/CKO mouse models, has revealed its significance in neurodegenerative diseases like amyotrophic lateral sclerosis, frontotemporal dementia, and tauopathy, as well as in inflammatory and autoimmune-related neurological conditions such as EAE. Understanding Tia1's functions provides insights into disease mechanisms and potential therapeutic targets.