LPIN

LPIN refers to the lipin gene family, comprising LPIN1, LPIN2, and LPIN3, which encode the Lipin-1, Lipin-2, and Lipin-3 proteins. In mammals, lipins function primarily as magnesium-dependent phosphatidic acid phosphatases that convert phosphatidic acid to diacylglycerol, a central step in triglyceride and phospholipid biosynthesis. In addition to their enzymatic activity, lipins serve as transcriptional coactivators that interact with lipid-regulated transcription factors such as PPARs and SREBP, influencing adipogenesis, fatty acid metabolism, and energy homeostasis. Subcellular localization is dynamic, with cytosolic and endoplasmic reticulum-associated pools supporting lipid synthesis, and nuclear pools modulating gene expression; phosphorylation status influences localization and activity and is responsive to nutritional and hormonal cues.

LPIN genes show tissue expression in adipose tissue, liver, and skeletal muscle, among others, consistent with roles in systemic lipid handling. Clinically, LPIN1 mutations cause a rare autosomal-recessive syndrome characterized by recurrent episodes of rhabdomyolysis and myoglobinuria, often triggered by exercise or fasting. LPIN2 mutations underlie Majeed syndrome, a recessive disorder featuring chronic recurrent multifocal osteomyelitis and dyserythropoietic anemia. LPIN3 has fewer characterized disease associations, but remains studied as a contributor to lipid metabolism.

Ongoing research investigates LPIN involvement in obesity, insulin resistance, hepatic steatosis, and inflammatory processes, as well as the potential of targeting lipin pathways for metabolic disease therapies.