LPIN1

LPIN1 is a human gene that encodes lipin-1, a member of the lipin family of proteins involved in lipid metabolism. Lipin-1 has enzymatic phosphatidic acid phosphatase (PAP) activity, converting phosphatidic acid to diacylglycerol, a key step in triglyceride and phospholipid biosynthesis. In addition to its cytosolic enzymatic role, lipin-1 can function as a transcriptional coactivator for lipid-regulating transcription factors such as PPARs and PGC-1alpha, linking lipid synthesis to gene expression. The protein is broadly expressed, with notable levels in adipose tissue, skeletal muscle, and liver, and exists in multiple isoforms generated by alternative splicing.

Biologically, lipin-1 participates in adipogenesis and the regulation of triglyceride storage and fatty acid oxidation. Its activity and localization are influenced by nutritional and hormonal signals and by phosphorylation, which can regulate shuttling between the cytosol and nucleus.

Clinical significance, pathogenic variants in LPIN1 cause LPIN1-related acute recurrent rhabdomyolysis, a severe autosomal recessive myopathy characterized by recurrent episodes of muscle breakdown, often triggered by febrile illness or strenuous exercise in children. Affected individuals typically present with muscle pain, weakness, and elevated serum creatine kinase during attacks; management emphasizes avoidance of triggers and prompt treatment of rhabdomyolysis, along with genetic counseling.

Evolution and family, LPIN1 is part of the vertebrate lipin gene family, which also includes LPIN2 and LPIN3, encoding lipin-2 and lipin-3 with related roles in lipid metabolism.