biostudies-literatureBormann AGerman Research FoundationUniversity of Leipzig Faculty of Medicine104348https://www.ebi.ac.uk/biostudies/studies/S-EPMC12860600biostudies-literatureUnknown7(1)Transmembrane proteins are notoriously difficult to isolate from tissue samples due to their hydrophobic nature and often low abundance. Here, we describe a protocol for the isolation, enrichment, and detection of the high-molecular-weight adhesion-type G protein-coupled receptor (aGPCR) member ADGRL/Latrophilin/Cirl from lipid-rich Drosophila melanogaster pupae. We detail steps to collect and homogenize pupae, enrich Cirl through immunoprecipitation, and visualize protein bands after SDS-PAGE and Western Blot. This protocol can be readily adapted to other tissues and (transmembrane) proteins. For complete details on the use and execution of this protocol, please refer to Bormann et al.¹.STAR protocolsProtocol for the isolation and immunoprecipitation of cell surface proteins from Drosophila melanogaster pupae.PMC12860600265903901421152132CRC 1423Bormann AScholz NBigl MfalseProtocol for the isolation and immunoprecipitation of cell surface proteins from Drosophila melanogaster pupae.Transmembrane proteins are notoriously difficult to isolate from tissue samples due to their hydrophobic nature and often low abundance. Here, we describe a protocol for the isolation, enrichment, and detection of the high-molecular-weight adhesion-type G protein-coupled receptor (aGPCR) member ADGRL/Latrophilin/Cirl from lipid-rich Drosophila melanogaster pupae. We detail steps to collect and homogenize pupae, enrich Cirl through immunoprecipitation, and visualize protein bands after SDS-PAGE and Western Blot. This protocol can be readily adapted to other tissues and (transmembrane) proteins. For complete details on the use and execution of this protocol, please refer to Bormann et al.¹.2026-01-01T00:00:00Z2026 Jan2026-06-18T03:08:15.622Z2026-06-18T03:07:15.275ZS-EPMC128606004158115310.1016/j.xpro.2026.104348