{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Jain A"],"funding":["NIAID NIH HHS","NCI NIH HHS","NIGMS NIH HHS"],"pagination":["eadq8331"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12832182"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["387(6741)"],"pubmed_abstract":["Breakdown of every transmembrane protein trafficked to lysosomes requires proteolysis of their hydrophobic helical transmembrane domains. Combining lysosomal proteomics with functional genomic datasets, we identified lysosomal leucine aminopeptidase (LyLAP; formerly phospholipase B domain-containing 1) as the hydrolase most tightly associated with elevated endocytosis. Untargeted metabolomics and biochemical reconstitution demonstrated that LyLAP is a processive monoaminopeptidase with preference for amino-terminal leucine. This activity was necessary and sufficient for the breakdown of hydrophobic transmembrane domains. LyLAP was up-regulated in pancreatic ductal adenocarcinoma (PDA), which relies on macropinocytosis for nutrient uptake. In PDA cells, LyLAP ablation led to the buildup of "],"journal":["Science (New York, N.Y.)"],"pubmed_title":["Leucine aminopeptidase LyLAP enables lysosomal degradation of membrane proteins."],"pmcid":["PMC12832182"],"funding_grant_id":["R35 GM149302","R01 GM112948","U54 AI170792","R01 CA260249"],"pubmed_authors":["Olzmann JA","Gupta S","Zhang J","Detomasi TC","von Linde T","Perera RM","Dawson DW","Zoncu R","Craik CS","Bommer G","Spacci M","Jain A","Rohweder P","Luo J","Citron YR","Lange M","Anderson D","Rademaker G","Heremans I","Hernandez GA"],"additional_accession":[]},"is_claimable":false,"name":"Leucine aminopeptidase LyLAP enables lysosomal degradation of membrane proteins.","description":"Breakdown of every transmembrane protein trafficked to lysosomes requires proteolysis of their hydrophobic helical transmembrane domains. Combining lysosomal proteomics with functional genomic datasets, we identified lysosomal leucine aminopeptidase (LyLAP; formerly phospholipase B domain-containing 1) as the hydrolase most tightly associated with elevated endocytosis. Untargeted metabolomics and biochemical reconstitution demonstrated that LyLAP is a processive monoaminopeptidase with preference for amino-terminal leucine. This activity was necessary and sufficient for the breakdown of hydrophobic transmembrane domains. LyLAP was up-regulated in pancreatic ductal adenocarcinoma (PDA), which relies on macropinocytosis for nutrient uptake. In PDA cells, LyLAP ablation led to the buildup of ","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Mar","modification":"2026-07-15T06:07:37.72Z","creation":"2026-07-01T03:07:43.812Z"},"accession":"S-EPMC12832182","cross_references":{"pubmed":["40146846"],"doi":["10.1126/science.adq8331"]}}