{
  "abstract": "Bis(monoacylglycero)phosphate (BMP), a lysosomal phospholipid essential for lipid catabolism and cholesterol clearance, has a noncanonical S,S glycerol configuration found in no other mammalian phospholipid, a feature necessary for its stability in the lysosome. How cells invert glycerol stereochemistry to build S,S-BMP has remained unexplained since this configuration was discovered five decades ago. Here, we show that the endoplasmic reticulum-resident Batten disease protein CLN6 is a Ca2+-dependent epimerase that isomerizes glycerophosphoglycerol (GPG) from R,S-GPG to S,S-GPG. CLN6-deficient cells, mouse tissues, and patient samples predominantly contain R,S-GPG, S,R-lysophosphatidylglycerol (LPG), and R,S-BMP instead of their S,S counterparts, with a net depletion of BMP. Purified CLN6 catalyzes GPG epimerization in vitro, an activity abolished by a pathogenic substitution in its substrate-binding pocket. Consistently, exogenous S,S-GPG restores BMP synthesis and relieves lipid storage in CLN6-null cells. Our work establishes stereochemical commitment upstream of acylation, placing CLN6, CLN8, and CLN5 in sequence in BMP biosynthesis and unifying the lipid defect across these neurodegenerative disorders.",
  "abstract_shown": true,
  "affiliations": [
    "Stanford University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "name": "Z. Zhu"
    },
    {
      "name": "J. Xiong"
    },
    {
      "name": "I. Maaz"
    },
    {
      "name": "M. J. Matrongolo"
    },
    {
      "name": "A. Ghoochani"
    },
    {
      "name": "C. Chilkunda"
    },
    {
      "name": "X. Peng"
    },
    {
      "name": "A. Alur"
    },
    {
      "name": "C. Porsen"
    },
    {
      "name": "A. Schulz"
    },
    {
      "name": "S. Cotman"
    },
    {
      "name": "N. Gomez-Ospina"
    },
    {
      "affs": [
        0
      ],
      "name": "M. Abu-Remaileh"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6wmn89z1hehn2.bib",
  "cited_by": 1,
  "doi": "10.64898/2026.10.07.757477",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.07.757477v1.full",
  "id": "6wmn89z1hehn2",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.07.757477v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biochemistry"
    ],
    [
      "openalex",
      "2737|Lysosomal Storage Disorders Research"
    ]
  ],
  "openalex": "W7221170260",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.07.757477v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-07",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6wmn89z1hehn2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:26:47Z",
      "native_id": "10.64898/2026.10.07.757477",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.07.757477v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Lysosomal Storage Disorders Research",
      "subfield": "physiology"
    }
  ],
  "title": "The Batten disease gene product CLN6 is a glycerophosphoglycerol epimerase that establishes S,S-BMP stereochemistry",
  "title_text": "The Batten disease gene product CLN6 is a glycerophosphoglycerol epimerase that establishes S,S-BMP stereochemistry",
  "type": "preprint",
  "updated_at": "2026-10-30T12:26:47Z",
  "url": "https://research.draconitic.com/paper/6wmn89z1hehn2",
  "venue": "bioRxiv",
  "versions": []
}