Recent insights into lysosomal acid lipase deficiency

Trends Mol Med. 2023 Jun;29(6):425-438. doi: 10.1016/j.molmed.2023.03.001. Epub 2023 Apr 5.


Lysosomal acid lipase (LAL) is the sole enzyme known to degrade neutral lipids in the lysosome. Mutations in the LAL-encoding LIPA gene lead to rare lysosomal lipid storage disorders with complete or partial absence of LAL activity. This review discusses the consequences of defective LAL-mediated lipid hydrolysis on cellular lipid homeostasis, epidemiology, and clinical presentation. Early detection of LAL deficiency (LAL-D) is essential for disease management and survival. LAL-D must be considered in patients with dyslipidemia and elevated aminotransferase concentrations of unknown etiology. Enzyme replacement therapy, sometimes in combination with hematopoietic stem cell transplantation (HSCT), is currently the only therapy for LAL-D. New technologies based on mRNA and viral vector gene transfer are recent efforts to provide other effective therapeutic strategies.

Keywords: LAL-D; LIPA; Wolman disease; acid lipolysis; cholesteryl ester storage disease; lysosomal lipid storage disorder.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Lipids / therapeutic use
  • Sterol Esterase / genetics
  • Sterol Esterase / metabolism
  • Wolman Disease* / diagnosis
  • Wolman Disease* / genetics
  • Wolman Disease* / therapy


  • Sterol Esterase
  • Lipids

Supplementary concepts

  • Lysosomal acid lipase deficiency