Lipa, encoding lysosomal acid lipase, is crucial for the hydrolysis of both triglycerides and cholesteryl esters in the lysosome [2]. This process is integral to lipid metabolism, and Lipa's function is vital for maintaining normal lipid levels and lipoprotein composition in the body. Genetic models, such as gene knockout in mice, can be used to study its function.

Mutations in the Lipa gene lead to LAL deficiency (LAL-D), with severe subtypes like Wolman disease [2]. In a study on Egyptian patients, a novel missense variant in the Lipa gene was identified, expanding the spectrum of variants involved in WD [2]. In patients with cholesteryl ester storage disease (CESD) due to Lipa gene mutations, there are significant changes in plasma levels and lipid composition of lipoproteins, increasing cardiovascular risk [1]. Exercise-induced improvement of lipid droplet metabolism disorder in a mouse model of non-alcoholic fatty liver disease involves upregulation of Lipa expression, suggesting its role in lipid metabolism regulation [3].

In conclusion, Lipa is essential for lipid metabolism. Studies on Lipa-related gene mutations and its role in various disease models, such as in Wolman disease, CESD, and non-alcoholic fatty liver disease, have enhanced our understanding of its function in maintaining normal lipid homeostasis and the pathophysiology of associated diseases.

References:

1. Arnaboldi, Lorenzo, Ossoli, Alice, Giorgio, Eleonora, Calabresi, Laura, Gomaraschi, Monica. 2020. LIPA gene mutations affect the composition of lipoproteins: Enrichment in ACAT-derived cholesteryl esters. In Atherosclerosis, 297, 8-15. doi:10.1016/j.atherosclerosis.2020.01.026. https://pubmed.ncbi.nlm.nih.gov/32058863/

2. Elaraby, Nesma M, Galal, Eman Reda, Abdel-Hamid, Mohamed, Mounir, Samir M, Ashaat, Engy A. 2023. First LIPA Mutational Analysis in Egyptian Patients Reveals One Novel Variant: Wolman Disease. In Journal of molecular neuroscience : MN, 73, 598-607. doi:10.1007/s12031-023-02139-6. https://pubmed.ncbi.nlm.nih.gov/37470904/

3. Fang, Chunlu, Liu, Shujing, Yang, Wenqi, Peng, Shuang, Li, Liangming. 2024. Exercise ameliorates lipid droplet metabolism disorder by the PLIN2-LIPA axis-mediated lipophagy in mouse model of non-alcoholic fatty liver disease. In Biochimica et biophysica acta. Molecular basis of disease, 1870, 167045. doi:10.1016/j.bbadis.2024.167045. https://pubmed.ncbi.nlm.nih.gov/38306800/