ATRAID (all-trans retinoic acid-induced differentiation factor) is a membrane-associated protein that localizes to cytoplasmic vesicles, the Golgi apparatus, and endosomal/lysosomal compartments 1. Its primary function involves promoting osteoblast differentiation and bone mineralization while inhibiting osteoblast proliferation through CCND1 downregulation in the retinoic acid signaling pathway. ATRAID forms a critical transporter complex with SLC37A3 to enable cytosolic entry of nitrogen-containing bisphosphonates (N-BPs) from lysosomes, a mechanism essential for N-BP pharmacological action in osteoclasts 2. Loss of ATRAID function confers cellular resistance to N-BP-mediated effects and impairs therapeutic responses to bisphosphonates in osteoporosis models 3. Clinically, ATRAID variants are associated with atypical femoral fractures and osteonecrosis of the jaw in bisphosphonate-treated patients, suggesting genetic susceptibility to these adverse effects 435. Additionally, ATRAID variants show causal associations with functional outcomes after ischemic stroke and benign prostatic hyperplasia through Mendelian randomization analyses 67, and with variable drug response in acute myeloid leukemia 8. These findings position ATRAID as a key regulator of bone metabolism and a potential therapeutic target for bisphosphonate-related complications.