HTRA1

HTRA1 (HtrA Serine Peptidase 1), also termed PRSS11, is a secreted serine protease that modulates extracellular matrix (ECM) homeostasis and TGF-β signaling. It combines protease activity with a PDZ domain, enabling cleavage of ECM proteins (e.g., fibronectin, collagen) and suppression of TGF-β pathways by degrading ligands or receptors. This dual function links HTRA1 to TGF-β/Smad, MAPK, and Wnt signaling cascades. Clinically, HTRA1 dysregulation is implicated in age-related macular degeneration (AMD), cerebral amyloid angiopathy, osteoarthritis, and cancers (colorectal, ovarian). Loss-of-function mutations cause CARASIL, a hereditary cerebral small vessel disease. Drug development focuses on inhibiting its protease activity, with small molecules (KY-05009) and monoclonal antibodies (RG6147) in preclinical or early clinical trials for AMD and fibrotic diseases.