Testican-2 (SPOCK2): A multifunctional matricellular regulator

Testican-2 (SPOCK2) is a secreted, extracellular matrix-associated proteoglycan that modulates cell-matrix interactions, extracellular proteolysis, and tissue-specific signaling across multiple organs. Beyond its initial characterization in the central nervous system, subsequent studies have established roles in the lung, pancreas, bone, and kidney, where testican-2 regulates tissue remodeling and extracellular matrix dynamics under both physiological and disease conditions. Mechanistic, genetic, and proteomic studies highlight its dual role as a biomarker and functional modulator, with kidney disease emerging as a clinically relevant context. However, upstream regulators, cell-type-specific functions, context-dependent effects, and the structural basis underlying its domain-specific interactions remain to be fully defined. This review synthesizes current evidence on testican-2 biology across tissues and disease settings, highlighting emerging themes and unresolved questions. A clearer understanding of its regulation and function will help refine its value as a biomarker and potential therapeutic target.