EPYC (epiphycan) is a small leucine-rich repeat proteoglycan primarily involved in extracellular matrix organization and structural development. In normal physiology, EPYC functions in bone and cartilage formation through matrix organization and glycosaminoglycan binding 1. However, EPYC has emerged as a significant biomarker in multiple pathological contexts. In intervertebral disc degeneration, EPYC serves as a specific cell-type biomarker for nucleus pulposus and inner annulus fibrosis cells 2. EPYC is downregulated in osteoarthritis, where its silencing associates with disease occurrence and altered immunocyte infiltration 1. Conversely, EPYC is aberrantly upregulated in several malignancies: in pancreatic cancer, EPYC promotes cell proliferation via PI3K-AKT signaling and functions as an independent poor prognostic factor 3; in gastric cancer, NSUN2-mediated m5C modification of EPYC stabilizes its mRNA, promoting cell growth and metastasis while restraining apoptosis and ferroptosis 4; in osteosarcoma, EPYC is part of an arachidonic acid metabolism-related gene signature predicting poor prognosis 5; and in ovarian cancer, EPYC is overexpressed in bowel metastases, correlating with incomplete cytoreduction 6. Notably, EPYC mutations do not contribute significantly to high myopia 7, and coding region mutations were excluded in posterior amorphous corneal dystrophy 8.