Testican-2: from glomerular activity to circulating biomarker

Testican-2, encoded by SPOCK2, is a secreted extracellular matrix-associated proteoglycan involved in podocyte and glomerular biology. The kidney contributes to the circulating Testican-2 pool, with podocytes representing a major renal source. Higher circulating levels are generally associated with better-preserved kidney function, less proteinuria, more favorable renal outcomes, and milder glomerular pathology, although these relationships vary across disease settings. In vitro and rodent studies show that Testican-2 binds vitronectin, restrains excessive integrin αVβ3 activation, and attenuates podocyte and filtration barrier injury. However, plasma abundance cannot yet be assumed to reflect the biologically active glomerular pool, because circulating levels may also be influenced by extracellular retention, glycosylation, proteolytic processing, and clearance. This uncertainty limits both biomarker interpretation and therapeutic translation. This Mini Review integrates clinical and experimental evidence to clarify what circulating Testican-2 may represent and identify the studies needed to connect plasma measurements with local glomerular activity.