Emerging research has shown important roles of lncRNAs in various forms of gene-regulation. However, they are still underexplored as direct or indirect modifiers in development or progression of DKD. Identifying novel lncRNAs in DKD and exploring their functional and mechanistic roles will advance our knowledge on potential pathogenic roles of these novel targets and lead to new therapeutic strategies in DKD. Our aim: identify novel, differentially-expressed lncRNAs, common to mouse-models of DKD, and prioritise only the most highly upregulated lncRNAs for validation and functional assessments. RNA-sequencing and bioinformatics (AGRF) were performed to identify novel, differentially-expressed lncRNAs, common to both types of DKD, in two C57Bl/6 mouse-models of DKD (n=3 per-group) -Type 1 (streptozotocin (STZ)-induced) and Type 2 (high-fat-diet (HFD) and obese), compared to control. Validation studies were performed by qPCR in diabetic mouse kidney and PTCs exposed to HG (30mM) and TGF-β1 (2 or 5ng/ml) in HK-2 and primary culture of mouse kidney PTCs. Agarose gel-electrophoresis confirmed PCR-product and Sanger-sequencing was performed. Genomic annotation browsers were explored to identify candidate lncRNA's flanking-genes. Mechanistic studies explored candidate lncRNA using sequence-specific LNA-GapmeRs (Exiqon) in kidney PTCs exposed to TGF-β1. Large number of differentially-expressed genes (DEGs) were identified by RNA-seq and bioinformatics, among which four novel, most highly upregulated lncRNAs (log2FC>1, P<0.05), common to both models of DKD: 3300005D01Rik, Gm10603, Gm20045, Gm26684. Validation studies using qPCR confirmed only lncRNA Gm10603 consistently expressed in both mouse and human kidneys, and different kidney cell-types. Importantly, it consistently expressed in kidney PTCs. Hence, Gm10603 was prioritised for further investigation. Sanger-sequencing confirmed high similarity of Gm10603-PCR-product between mice and humans, and conservation and synteny determined with its flanking genes: C2cd3, Ucp2, Ucp3. Gm10603 was upregulated in STZ-induced DKD mouse kidney compared to control (n=11,***P=0.0001), a non-significant rise in HFD-induced DKD (n=8-11,P=0.10). TGFβ-1 upregulated Gm10603 in mouse PTCs (n=8,**P<0.01), HK-2 (n=5,*P<0.05) at 48hr, and less by HG in HK-2 (n=4,P=0.07) at 48hr. There was the same pattern of regulation by TGF-β1 in PTCs with its flanking-genes. TGF-β1 upregulated C2cd3 in mouse PTCs (n=7,**P<0.01) and HK-2 (n=3,*P<0.05) at 48hr and Ucp2 at 7days (n=4,*P<0.05). Using Gm10603-sequence-specific LNA-GapmeRs (Exiqon), some reduction of Gm10603-mRNA was observed by Gm10603-knockdown in the presence of TGF-β1, however no consistent reduction in inflammatory and pro-fibrotic markers and flanking genes. (Acknowledgement to Prof. U. Panchapakesan for RNA-sequencing and identification of target genes) Our study suggests novel antisense lncRNA Gm10603 is common pathogenic lncRNA in DKD, driven by TGF-β1 in mouse and human kidney PTCs. Both Gm10603 and its flanking genes C2cd3 and Ucp2 were dysregulated in DKD. While knockdown of Gm10603-expression in the presence of TGF-β1 somewhat reduced Gm10603, there was no consistent attenuation of fibrotic or inflammatory markers by both Gm10603-LNA-GapmeRs. Hence, there may be a partial effect or other mechanisms involved. Further exploration of this novel lncRNA is required.