CRTAC1 in extracellular matrix remodeling and calcium signaling: Implications for disease and biomarker development.

Cartilage acidic protein 1 (CRTAC1) has recently emerged as a molecule of interest across multiple pathological contexts, particularly in degenerative diseases such as osteoarthritis (OA), as well as in selected pulmonary and malignant conditions. Originally described as a cartilage-associated extracellular matrix (ECM) protein, CRTAC1 is also expressed in other tissues, including lung and bladder, suggesting broader biological functions. Two major isoforms have been identified, with CRTAC1-A predominating in peripheral tissues. Accumulating evidence indicates that CRTAC1 is associated with ECM remodeling and may influence cell-matrix interactions through integrin binding and modulation of calcium-dependent signaling pathways. Experimental studies suggest that CRTAC1 can affect intracellular calcium flux, oxidative stress responses, and stress kinase activation, including p38 MAPK and JNK pathways, contributing to context-dependent regulation of cell survival and apoptosis. However, the extent to which these mechanisms directly translate into in vivo disease processes remains unclear. Clinically, CRTAC1 shows the strongest evidence as a biomarker in OA, where large-scale proteomic studies consistently associate elevated plasma levels with disease severity, progression, and risk of joint replacement. In contrast, findings in pulmonary diseases and cancer are more heterogeneous and appear to be context-dependent. Overall, CRTAC1 represents a promising biomarker candidate, particularly in degenerative joint disease, while its mechanistic roles and broader clinical applicability require further validation through standardized and large-scale studies.