Plod1, also known as procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1, is a collagen-related lysyl hydroxylase. It is involved in important biological processes, and its associated pathways include Wnt/β-catenin, HSF1, Hippo-YAP, SOX9/PI3K/Akt/mTOR, and NF-κB signaling pathways. It plays a role in various physiological and pathological conditions, especially in cancer development and vascular diseases [1-9].

In multiple cancer types, loss-of-function experiments have provided insights into Plod1's role. In thyroid carcinoma (THCA), si-Plod1 inhibited cell proliferation, migration, and glycolysis, reversing the effects induced by the transcription factor MAZ on cell activities through the Wnt/β-catenin pathway [1]. In glioma, targeted depletion of Plod1 suppressed U87 cell proliferation and colony formation by inactivating the HSF1 signaling pathway [3]. In osteosarcoma, down-regulation of Plod1 inhibited cell proliferation, migration, and invasion, and it was found to inactivate the Hippo-YAP pathway by repressing LATS1 phosphorylation [4,6]. In gastric cancer, knockdown of Plod1 decreased cell viability and aerobic glycolysis by regulating the SOX9/PI3K/Akt/mTOR signaling pathway [5]. In glioblastoma, over-expression of Plod1 promoted the malignant phenotype, and its depletion could potentially reverse these effects via the NF-κB signaling pathway [7]. In a family with familial thoracic aortic aneurysm/dissection, a missense variant in Plod1 was identified, and in vitro studies using human aortic vascular smooth muscle cells with si-Plod1 showed hypercontractility and up-regulation of contractile markers, suggesting a role in vascular disease [2].

In conclusion, Plod1 is crucial in multiple biological processes, especially in cancer and vascular diseases. Model-based research, particularly loss-of-function experiments, has revealed its role in promoting cell proliferation, migration, invasion, and glycolysis in cancer, as well as its potential involvement in vascular smooth muscle cell phenotypic switching in vascular disease. Understanding Plod1's function provides potential therapeutic targets for these diseases.