Current findings indicate that HTRA1 is not only present extracellularly as a secretory protein, but also found intracellularly and is associated with microtubules to regulate cell migration.2 HTRA1 takes part in many biological processes and cellular signalling pathways, and is implicated in pathogenesis including osteoporosis, osteoarthritis, Alzheimer's disease, age‐related macular degeneration and cancer.3, 4, 5, 6 This topical review discusses recent findings pointing to the role of HTRA1 in bone biology, arthritis and tumorigenesis. This evidence concerns the gene HTRA1 and osteoporosis.