SLC35B1 is a primary ATP/ADP exchanger localized to the endoplasmic reticulum (ER) membrane that mediates stepwise ATP translocation from the cytosol into the ER lumen 1. The protein operates through strict ATP/ADP antiport, displaying asymmetrical affinities with approximately 13-fold higher affinity for nucleotides on the internal ER face compared to the external cytosolic face 2. Beyond ATP/ADP exchange, SLC35B1 functions as a broad-range di- and tri-nucleotide exchanger, also transporting UDP-glucuronic acid (UDPGA) and UDP-galactose 34. Mechanistically, SLC35B1 provides essential ATP to support ER-resident Hsp70 chaperone BiP, which is critical for protein folding and quality control 5. ATP import into the ER is regulated by a calcium-dependent mechanism antagonized by elevated cytosolic Ca2+, integrating mitochondrial ATP supply with ER calcium signaling 6. In hepatic metabolism, SLC35B1-mediated UDPGA transport significantly modulates UDP-glucuronosyltransferase (UGT) activity, making it the primary transporter of UDPGA in human liver 3. Clinically, SLC35B1 is essential for cell viability, clustering with critical SLC transporters 1. Dysregulation of SLC35B1 expression has been identified as a potential diagnostic marker in endometriosis and recurrent implantation failure 7, and altered SLC35B1 levels appear in breast cancer plasma proteomes 8.