Arginine vasopressin (AVP) and one of its G protein-coupled receptors (GPCRs), V1A, have been of therapeutic interest for decades due to their stimulatory contractile effect on vascular smooth muscle. AVP and V1A have also been identified as targets to treat various neurological disorders, with V1A antagonists showing therapeutic promise for treating aspects of autism spectrum disorder1. Despite this interest, the therapeutic potential of V1A remains unfulfilled, with no approved drugs specifically targeting V1A. The design and optimisation of new drugs, and our understanding of how AVP interacts with V1A, is limited by the lack of experimental structures of the vasopressin-oxytocin receptor family. GPCR structural biology is a rapidly developing field, however the low-expression level and instability of many GPCRs, including V1A, can be problematic for purification and subsequent structural study. Engineering high-expressing, stabilised, receptor mutants has been successful for structural biology campaigns against other neuropeptide receptors, including neurotensin receptor 1 (NTS1)2. Engineering high-expressing receptor involves the generation of a diverse library of receptor mutants, which are then expressed in cells and screened for high-expression using fluorescent-activated cell sorting (FACS). To date, this method has relied on bacteria and yeast cell display, however not all GPCRs can be expressed in these hosts. To overcome these issues, we developed a mammalian cell display technique using lentivirus as the gene-delivery method. Using this method, V1A mutants were screened for high cell-surface expression using a receptor-specific fluorescent ligand, which isolated V1A mutants that exhibited a 25-fold increase in expression compared to wild-type. Selected receptors contained only 2-3 mutations and displayed similar ligand-binding and signalling characteristics to wild-type V1A. Further mutagenesis and screening rounds are to be conducted and these high-expressing V1A mutants are to be purified, and their stability tested. Beneficial mutations with a contribution to receptor stability will facilitate purification and structural study of this important therapeutic target.