The emerging role of eIF5A hypusination as a unique and underexplored mechanism in proteinopathies and neurological diseases.

Eukaryotic Translation Initiation Factor 5A (eIF5A) undergoes a unique post-translational modification of hypusination, converting a lysine 50 residue to hypusine (hypK50). While a few studies have investigated the role of the spermidine-hypusine-eIF5A axis in neurodegenerative diseases, including the pathological accumulation of tau and TAR DNA-binding protein 43 (TDP-43), the role of the hypusine pathway in neurological diseases remains vastly understudied. Thus, the focus of this review is highlighting emerging research on the mechanisms by which aberrant and chronic increases in hypusinated eIF5A (eIF5A) govern nucleocytoplasmic transport, stress granule dynamics, and protein aggregation to encourage further research of this pathway in multi-etiology dementia.