ACP5 (acid phosphatase 5, tartrate-resistant) is a multifunctional enzyme with critical roles in bone metabolism and immune regulation. Primarily, ACP5 dephosphorylates skeletal phosphoproteins including osteopontin and bone sialoprotein, and is expressed by osteoclasts, macrophages, and dendritic cells 1. Mechanistically, ACP5 expression is regulated by RANKL through NFATc1 and c-Fos pathways 2, and its phosphatase activity on β-catenin promotes fibroblast differentiation and proliferation in pulmonary fibrosis 3. ACP5 also regulates macrophage/microglia polarization and proinflammatory responses 4. Disease relevance spans skeletal and inflammatory disorders. Elevated ACP5 levels correlate with idiopathic pulmonary fibrosis severity 3, and ACP5 inhibition protects against bleomycin-induced lung fibrosis and osteoporosis 5 6. In acute ischemic stroke, ACP5 promotes macrophage/microglia-driven neuroinflammation, and its inhibition by quercetagetin ameliorates brain injury 4. Clinically, ACP5 serves as a therapeutic target. ACP5 silencing, pharmacological inhibition, or specific inhibitors (including natural products) represent promising approaches for treating pulmonary fibrosis, osteoporosis, and stroke 3 4. Notably, ACP5 functions beyond bone—contributing to immune cell biology, oxidative stress regulation, and inflammatory diseases—suggesting broader therapeutic potential.