Ddr1, short for Discoidin domain receptor 1, is a collagen-activated receptor tyrosine kinase. It plays a crucial role in regulating various vital processes such as cell differentiation, proliferation, adhesion, migration, invasion, and matrix remodeling [1]. It is involved in multiple signaling pathways, for example, the DDR1-NF-κB-p62-NRF2 pathway in pancreatic cancer [3]. Given its roles in numerous biological processes, genetic models like gene knockout (KO) or conditional knockout (CKO) mouse models are valuable for studying its functions.

In tumor-related studies, ablation of Ddr1 in tumors promotes intratumoral penetration of T cells and obliterates tumor growth in mouse models of triple-negative breast cancer (TNBC), indicating its role in instigating immune exclusion [2]. In pancreatic ductal adenocarcinoma (PDAC), matrix-metalloprotease-cleaved Col I activates DDR1-NF-κB-p62-NRF2 signaling to promote tumor growth, while intact Col I triggers DDR1 degradation and restrains growth [3]. In hepatocellular carcinoma (HCC), collagen I-DDR1 signaling promotes cancer cell stemness [4]. In kidney-related research, Ddr1-null mice have reduced acute tubular injury, inflammation, and tubulointerstitial fibrosis after ischemia/reperfusion-induced acute kidney injury, suggesting DDR1 contributes to kidney inflammation and fibrosis [5].

In conclusion, Ddr1 is essential in regulating multiple biological processes. Studies using Ddr1 KO/CKO mouse models have revealed its significant roles in various disease areas, including cancer and kidney diseases. These models have provided valuable insights into the functions of Ddr1, helping to understand the mechanisms of disease occurrence and potentially offering new therapeutic targets.