Fused in Sarcoma (FUS), Ewing Sarcoma (EWSR1) and TATA-Box Binding Protein Associated Factor 15 (TAF15) are conserved RNA binding proteins that make up the FET family. In Amyotrophic Lateral Sclerosis (ALS), mutations in FUS lead to its cytoplasmic mislocalisation and the formation of cytoplasmic inclusion in neurons. However, in Frontotemporal Dementia (FTD), inclusions are made up of all three FET proteins along with their nuclear import receptor TNPO1 in the absence of any mutation.This project aims to characterise the spatio-temporal expression of the FET proteins in the central nervous system (CNS) of non-transgenic mice through aging, ultimately forming the basis for comparative analysis of FET expression between FUS-ALS and FET-FTD patient tissues and healthy controls.A combination of high-throughput microscopy and quantitative reverse transcription polymerase chain reaction (RT-qPCR) were used to map the expression of FET proteins in 3,12 and 24 month non-transgenic (Ntg) C57BL6 mice CNS and mouse embryonic stem cells. This was accompanied by comparisons of vulnerable and resistant patient tissues.We see clear differences in FET protein levels and sub-cellular localisation across the whole brain and spinal cord of Ntg mice throughout aging, along with differential FET gene expression. Endogenous EWSR1 and TAF15, show differential localisation when FUS inclusions are seen in ALS patient tissue. While we observe mislocalisation of FET proteins in FTD, we also notice differential inclusion signatures being displayed. This project provides insight into why protein inclusions differ between the diseases in order to understand the specific cell vulnerability in FUS-ALS and FET-FTD.