Serine protease with a variety of targets, including extracellular matrix proteins such as fibronectin. HTRA1-generated fibronectin fragments further induce synovial cells to up-regulate MMP1 and MMP3 production. May also degrade proteoglycans, such as aggrecan, decorin and fibromodulin. Through cleavage of proteoglycans, may release soluble FGF-glycosaminoglycan complexes that promote the range and intensity of FGF signals in the extracellular space. Regulates the availability of insulin-like growth factors (IGFs) by cleaving IGF-binding proteins. Inhibits signaling mediated by TGF-beta family members. This activity requires the integrity of the catalytic site, but it is unclear whether it leads to the proteolytic degradation of TGF-beta proteins themselves (PubMed:18551132) or not (PubMed:14973287). By acting on TGF-beta signaling, may regulate many physiological processes, including retinal angiogenesis and neuronal survival and maturation during development. Intracellularly, degrades TSC2, leading to the activation of TSC2 downstream targets. Forms homotrimers. In the presence of substrate, may form higher-order multimers in a PDZ-independent manner (By similarity). Interacts with TGF-beta family members, including BMP4, TGFB1, TGFB2, activin A and GDF5. Predominantly secreted. Also found associated with the plasma membrane. In the brain, mainly expressed in cortical areas both in glial cells and neurons (at protein level). In bones, deposited in the matrix, with higher level in newly formed bone compared to fully calcified bone (at protein level). Also expressed in the tendons (at protein level). In the articular cartilage, detected only in the deepest zone of the joint cartilage. Not detected in the chondrocytes of the growth plate (at protein level). In an experimental arthritis model, at early disease stages, up-regulated in articular chondrocytes in the deep layers of the cartilage (at protein level). As arthritis progresses, chondrocyte expression expands toward the surface. First detected at 10.5 dpc. At 11.5 dpc, in the developing heart, expressed in the atrioventricular endocardial cushion and the outflow tract (at protein level). At 14.5 dpc, strong expression in the outflow tracts, including valves. In the developing skeleton, expressed at 12.5 dpc in the vertebral column and limbs. At 14.5 dpc, expressed in rudiments of tendons and ligaments along the vertebrae, as well as in mesenchymal cells surrounding precartilage condensations. Not detected in precartilage condensations, nor in chondrocytes, but strongly expressed in ossification centers. At 17.5 dpc, in the hind limb, significant expression persists in tendons and ligaments, but expression in the forming joints is reduced. At this stage, weakly detected in the thin layer of articular surfaces. Postnatally, in long bones, expressed by terminally differentiated hypertrophic chondrocytes that are committed to degeneration and eventually replaced by bone, as well as by osteoblasts at late differentiation stages and by mature osteocytes. In the developing brain, expressed in specific regions of the neuroepithelium in the forebrain and hindbrain adjacent to the forming choroid plexus. From 17.5 dpc till birth, expressed in neurogenic areas including ventricular zones (at protein level). At 12.5 and 14.5 dpc, expressed in Muellerian duct cells and in the surrounding mesenchyme in both male and female gonads. In the lung, detected in the mesenchymal cells. Expressed at 12.5 dpc in abdominal skin, both in epidermis and dermis. Also expressed in the epithelium of developing whiskers at 14.5 dpc. At later stages, localized in the basal layer of epidermis and in the invading epidermal cells that formed the whisker rudiments (at protein level). 9 days after birth, detected in the whisker outer root sheet (at protein level). The IGFBP N-terminal domain mediates interaction with TSC2 substrate. Mutants mice exhibit reduced retinal capillary density, as compared to wild type animals, in all 3 retinal layers, nerve fiber layer, as well as inner and outer plexiform layers. Belongs to the peptidase S1C family.