Compared to other organs the cells of the renal inner medulla are challenged with an environment of highly variable osmolality. Cellular adaption to changing osmolality is associated with changes in gene expression of osmoprotective genes. We performed a gene expression profiling using primarily cultured rat renal inner medullary collecting duct cells (IMCD) which were cultivated for 6 days at 300, 600 or 900mosmol/kg to identify novel genes and pathways that are affected. Compared to cells cultivated at 300 mosmol/kg at higher osmolality several genes were differentially expressed, including many known genes. An interesting gene which has not been described so far was the Ran Binding Protein 3 Like (RanBP3L). RanBP3L shows homologies to RanBP proteins which are involved in nuclear import and export. Realtime PCR showed that in comparison to 300mosmol/ kg RanBP3L has in adapted cells a 58-fold higher expression at 600mosmol/kg and a 360-fold higher expression at 900mosmol/kg. A 24 hour increase of osmolality from 300 to 600 respectively 600 to 900mosmol/kg showed an 85-fold respectively 12-fold RanBP3L increase. This indicates that RanBP3L plays a role both in the long-term adaption to a higher osmolality and during the phase of adapting to a higher osmolality. As a GFP fusion protein RanBP3L is expressed in the nucleus in HEK293 cells. An anti-RanBP3L generated antibody showed nuclear accumulation of RanBP3L in IMCD cells at high osmolality. These results indicate an important role of RanBP3L for the adaptation to high osmolality.