RSC1A1 encodes RS1, a 67-kDa intracellular regulatory protein that controls transporter trafficking through both transcriptional and post-transcriptional mechanisms 1. RS1 primarily regulates the Na+-D-glucose cotransporter SGLT1 by inhibiting dynamin and PKC-dependent exocytotic pathways, preventing vesicle release from the trans-Golgi network to reduce plasma membrane transporter abundance 12. The protein exhibits glucose-dependent regulation, with its inhibitory effects on SGLT1 and organic cation transporter OCT2 being reduced at higher intracellular glucose concentrations 1. RS1 localizes to the plasma membrane, trans-Golgi network, and nucleus, with nuclear migration appearing to regulate transcriptional control of SGLT1 3. Functionally, RS1 contains a regulatory domain (RS1-Reg) with multiple phosphorylation sites that differentially controls exocytotic pathways for different transporters in a phosphorylation-dependent manner 4. The physiological importance of RSC1A1 is demonstrated in knockout mice, which show sevenfold upregulation of intestinal SGLT1, increased glucose absorption, and development of obesity 5. These findings establish RSC1A1 as a critical regulator of glucose homeostasis with potential therapeutic implications for diabetes treatment through peptide-based SGLT1 inhibition 64.