Much of our understanding of RNA-protein interactions, and how these interactions shape gene expression and cell state, have come from studies looking at these interactions in vitro or inside the cell. However, recent data demonstrates the presence of extracellular and cell surface-associated RNA such as glycosylated RNA (glycoRNA), suggesting an entirely new environment and cellular topology in which to study RNA-RNA binding protein (RBP) interactions. Here, we explore emerging ideas regarding the landscape of cell surface RNA and RBPs. We also discuss open questions concerning the trafficking and anchoring of RBPs to the cell surface, whether cell surface RBPs (csRBPs) directly interact with cell surface RNA, and how changes in the presentation of csRBPs may drive autoimmune responses. Copyright © 2025 Elsevier Ltd. All rights reserved.