COL10A1 encodes type X collagen, a structural protein produced by hypertrophic chondrocytes and localized to mineralization zones in hyaline cartilage, where it contributes to extracellular matrix tensile strength and skeletal development. In normal cartilage physiology, COL10A1 expression marks the hypertrophic stage of chondrocyte differentiation; during osteoarthritis progression, COL10A1 upregulation correlates with disease severity and is accompanied by loss of chondroprotective factors 1. At the population level, gnomAD v4.1 classifies COL10A1 as loss-of-function tolerant (LOEUF=0.85), reflecting viable heterozygous carriers; however, this is distinct from clinical pathogenicity—ClinVar documents 79 pathogenic variants associated with skeletal dysplasias including metaphyseal chondrodysplasia 2. Recent evidence reveals oncogenic functions in cancer. COL10A1 is upregulated in colorectal, lung, gastric, and pancreatic cancers, where it activates TGF-β1/Smad, MEK/ERK, and focal adhesion kinase signaling to drive proliferation, invasion, and epithelial-mesenchymal transition 3. In colorectal cancer, COL10A1-positive fibroblasts suppress immunity via the COL10A1/CD18/JAK1/STAT3 axis and promote M2 macrophage polarization 4. Similar pro-tumorigenic roles have been documented in breast cancer, where lncRNA HAGLROS stabilizes COL10A1 to enhance macrophage M2 polarization 5. For osteoarthritis and cartilage regeneration, blocking α2-adrenergic signaling with phentolamine suppressed COL10A1-mediated hypertrophy and promoted hyaline cartilage regeneration 6, while exosomal miR-26b-5p targeting COL10A1 ameliorated degeneration in murine models 7. These findings position COL10A1 as both a marker of disease progression and a tractable therapeutic target across skeletal and oncologic contexts.