{
  "abstract": "Lysosomal catabolism depends on bis(monoacylglycero)phosphate (BMP), a phospholipid with atypical S,S stereochemistry of unknown biosynthetic origin. CLN8 and CLN5 catalyze sequential acylation steps in BMP synthesis, and their loss of function causes Batten disease, a group of inherited neurodegenerative lysosomal storage disorders. Here we identify CLN6, a biochemically uncharacterized endoplasmic reticulum protein whose loss also causes Batten disease, as the calcium-dependent glycerophosphoglycerol epimerase that establishes BMP stereochemistry upstream of CLN8. CLN6 deficiency depletes BMP in cells, mice, and patient lysosomes, and reduces lysosomal hydrolase levels. BMP-precursor supplementation bypasses CLN6, restores BMP and increases hydrolase abundance in CLN6-deficient cells and mice. These findings place three Batten disease proteins in a single biosynthetic pathway and reveal BMP deficiency as a reversible cause of disrupted lysosomal hydrolase homeostasis.",
  "abstract_shown": true,
  "affiliations": [
    "MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 30,
  "authors": [
    {
      "name": "P. K. Sheokand"
    },
    {
      "name": "A. M. James"
    },
    {
      "name": "C. Posern"
    },
    {
      "name": "A. Singh Sahrawat"
    },
    {
      "name": "J. Breithofer"
    },
    {
      "name": "J. Ganellin"
    },
    {
      "name": "M. K. Proulx"
    },
    {
      "name": "S. K. Leese"
    },
    {
      "name": "K. Turner"
    },
    {
      "name": "D. Lacabanne"
    },
    {
      "name": "D. Bulfon"
    },
    {
      "name": "B. Jenkins"
    },
    {
      "name": "J. van der Kleij"
    },
    {
      "name": "H. E. Johnston"
    },
    {
      "name": "S. O. Lord"
    },
    {
      "name": "M. K. Basran"
    },
    {
      "name": "C. S. Yu"
    },
    {
      "name": "C. D. Booth"
    },
    {
      "name": "J. M. Weimer"
    },
    {
      "name": "A. Koulman"
    },
    {
      "name": "M. Jäättelä"
    },
    {
      "name": "E. R. S. Kunji"
    },
    {
      "name": "D. N. Palmer"
    },
    {
      "name": "N. L. Mitchell"
    },
    {
      "name": "J. Prudent"
    },
    {
      "name": "R. Zimmermann"
    },
    {
      "name": "K. Gruber"
    },
    {
      "name": "A. Schulz"
    },
    {
      "name": "M. P. Murphy"
    },
    {
      "affs": [
        0
      ],
      "name": "K. Petkevicius"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bsyqshjtf81ps.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.07.757350",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.07.757350v1.full",
  "id": "bsyqshjtf81ps",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.07.757350v1",
  "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": "W7221092801",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.07.757350v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-07",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bsyqshjtf81ps.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:26:50Z",
      "native_id": "10.64898/2026.10.07.757350",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.07.757350v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Lysosomal Storage Disorders Research",
      "subfield": "physiology"
    }
  ],
  "title": "CLN6 is a glycerophosphoglycerol epimerase in bis(monoacylglycero)phosphate biosynthesis",
  "title_text": "CLN6 is a glycerophosphoglycerol epimerase in bis(monoacylglycero)phosphate biosynthesis",
  "type": "preprint",
  "updated_at": "2026-10-30T12:26:50Z",
  "url": "https://research.draconitic.com/paper/bsyqshjtf81ps",
  "venue": "bioRxiv",
  "versions": []
}