HTRA1 itself cleaves a plethora of substrates and is linked to several pathogenic and developmental processes, including cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), AMD, Alzheimer’s disease, osteoarthritis, neuronal development, and tumor progression8,13,17–20. This evidence concerns the gene HTRA1 and osteoarthritis.