HtrA1 was shown to play an important physiological role in extracellular matrix homeostasis and to cleave a substantial number of its components, such as fibronectin, type III collagen, decorin, aggrecan but also intracellular proteins such as tubulin (Canfield et al., 2007, Chien et al., 2004, De Luca et al., 2003, Schmidt et al., 2016).The HtrA1 protein has been reported to be present in drusen deposits, a hallmark of AMD pathogenesis, and within RPE cells isolated from AMD patients, albeit in a small cohort of patients (Tuo et al., 2008). This evidence concerns the gene ACAN and age-related macular degeneration.