Soil salinity causes large productivity losses for agriculture worldwide. "Next-generation crops" that can tolerate salt stress are required for the sustainability of global food production. Previous research in Arabidopsis thaliana aimed at uncovering novel factors underpinning improved plant salinity tolerance identified the protein kinase AtCIPK16. Overexpression of AtCIPK16 enhanced shoot Na + exclusion and increased biomass in both Arabidopsis and barley. Here, a comparative transcriptomic study on Arabidopsis lines expressing AtCIPK16 was conducted in the presence and absence of salt stress, using an RNA-Seq approach, complemented by AtCIPK16 interaction and localisation studies. We are now able to provide evidence for AtCIPK16 activity in the nucleus. Moreover, the results manifest the involvement of a transcription factor, AtTZF1, phytohormones and the ability to quickly reach homeostasis as components important for improving salinity tolerance in transgenics overexpressing AtCIPK16. Furthermore, we suggest the possibility of both biotic and abiotic tolerance through AtCIPK16, and propose a model for the salt tolerance pathway elicited through AtCIPK16. PrxR) (Baxter et al. 2014; Mittler et al. 2011); c) osmotic adjusters that can maintain low intracellular osmotic potential in plants under salt stress (for example proline, glycine betaine, free amino acids, sugars, polyamines and polyphenols) (Rosa et al. 2009); d) phytohormones that can facilitate a broad array of adaptive responses and long distance signalling (such as abscisic acid, indole acetic acid, cytokinins, gibberellic acid, salicylic acid, brassinosteroids, jasmonates, ethylene) (Fahad et al. 2015; Peleg and Blumwald 2011; Ryu and Cho 2015); and e) salt sensors including those that sense cytosolic Ca 2+ changes resulting from changes in the cytosol due to salinity and communicate the effects to downstream activating proteins (calcineurin-B-like proteins; CBLs and CBL-interacting protein kinases; CIPKs, calcium-dependent protein kinases; CDPKs, calmodulins; CaMs, calmodulin-like proteins; CAMLs, etc.) (Shabala et al. 2015).