Epdr1, or Ependymin-Related Protein 1, is a protein-coding gene with diverse functions. It is involved in various biological processes such as cell adhesion, and is associated with pathways like the PI3K/AKT pathway [3,5,7]. It has significance in metabolism, immune evasion, angiogenesis, and cancer development [1,2,6]. Genetic models can be valuable to study its functions in more detail.

In pancreatic β-cells, Epdr1 silencing reduced glucose-stimulated insulin secretion (GSIS), suggesting it channels glycolysis-derived pyruvate to the mitochondrial TCA cycle to maintain glucose homeostasis in obese individuals [1]. In cancer, in hepatocellular carcinoma, it promotes PD-L1 expression and tumor immune evasion by inhibiting TRIM21-dependent ubiquitylation of IkappaB kinase-β [2]. In bladder cancer, its expression is up-regulated with advanced tumor stage and metastasis, and high expression is associated with shorter overall survival [3,4]. In epithelial ovarian cancer, it acts as a tumor-suppressor gene via the PI3K/AKT pathway, and its expression is negatively regulated by miR-429 [7]. In colorectal cancer, its up-regulation is related to staging and promotes cell proliferation, migration, and invasiveness [8].

In conclusion, Epdr1 plays essential roles in metabolism, especially in pancreatic β-cell function related to glucose homeostasis. In cancer, it has different roles depending on the cancer type, either promoting tumor progression as in bladder, hepatocellular, and colorectal cancers or acting as a tumor-suppressor as in epithelial ovarian cancer. Studies using loss-of-function models have been crucial in revealing these functions in specific biological processes and disease conditions.