Epdr1, or Ependymin-Related Protein 1, is a protein-coding gene with diverse functions. It has been associated with various biological processes such as mitochondrial respiration linked to thermogenesis in brown fat [1]. It is also involved in signaling pathways like the PI3K/AKT pathway, cytokine-receptor interaction, and apoptosis [3]. EPDR1 is important for maintaining glucose homeostasis as it can regulate β-cell metabolism and function. In addition, it plays a role in cell adhesion [3,4].

In β-cells, Epdr1 silencing in human islets and β-cell lines reduced glucose-stimulated insulin secretion (GSIS), while treatment with human EPDR1 protein increased GSIS. Metabolomics analysis in Epdr1-KD INS1 832/13 cells suggested diversion of glucose-derived pyruvate to lactate production and decreased malate-aspartate shuttle and the tricarboxylic acid (TCA) cycle activity [1]. In cancer research, in hepatocellular carcinoma, EPDR1 binds to E3 ligase TRIM21, disrupts its interaction with IkappaB kinase-β, enhances NF-κB-mediated transcriptional activation of PD-L1, mediates exhaustion of CD8+ T cells, and promotes tumor progression [2]. In bladder cancer, EPDR1 expression was up-regulated with advanced tumor stage and metastasis, and high expression was associated with shorter overall survival [3]. In epithelial ovarian cancer, EPDR1 was downregulated, and its overexpression suppressed cell proliferation, migration, and invasion through the repression of the PI3K/AKT signaling pathway [5].

In conclusion, Epdr1 has multifaceted functions. It is crucial for β-cell metabolism and function, which is essential for glucose homeostasis. In cancer, it can either promote or suppress tumor progression depending on the cancer type. Studies using techniques like gene silencing in cell lines, similar to the concept of a loss-of-function approach in gene knockout models, have revealed these roles, providing insights into its functions in normal biological processes and disease conditions such as diabetes-related β-cell function and various cancers.