Background: Narcolepsy with cataplexy is a neurological sleep disorder, which is believed to arise from the autoimmune destruction of hypocretin-producing neurons. The purinergic receptor P2Y₁₁ is associated with narcolepsy in genome-wide association studies, and P2RY11 sequencing has further revealed eight rare missense mutations associated with the disease. Some of these mutations alter the signaling properties of P2Y₁₁, but for some, no functional effects have been discovered so far. Methods: This study examined the surface expression of the eight narcolepsy-associated P2Y₁₁ mutations using an in vitro surface expression assay. Results: The assay showed excellent discrimination between cells transfected with tagged wild type and the untagged P2Y₁₁ receptor, proving complete specificity towards the 3HA-N-tag used for the assay. Our results show a decreased surface expression of the R307W P2Y₁₁ mutant and a surface expression similar to wild type for the other seven mutants. Conclusion: Based on the present findings, alteration in surface expression is not likely to play a role in how P2Y₁₁ influences narcolepsy pathogenesis. This is important because intact surface expression increases the usefulness of P2Y₁₁ as a future drug target.