Lipin1

Lipin-1 is a protein encoded by the LPIN1 gene in humans and a member of the lipin family. Lipin-1 has a dual role in lipid metabolism: it functions as a magnesium-dependent phosphatidic acid phosphatase that converts phosphatidic acid to diacylglycerol, a key step in triglyceride and phospholipid synthesis, and it also acts as a transcriptional coactivator that modulates expression of genes involved in lipid metabolism.

Localization to the cytoplasm supports its enzymatic activity, while nuclear lipin-1 participates in transcriptional regulation by interacting with factors such as PPARs and SREBPs. The protein exists in multiple isoforms generated by alternative splicing and is expressed in adipose tissue, liver, skeletal muscle, and other tissues.

Clinical significance: LPIN1 mutations cause lipin-1 deficiency, a hereditary disorder characterized by recurrent episodes of rhabdomyolysis with myoglobinuria, often precipitated by fever, strenuous exercise, or fasting. Episodes may present with muscle pain, weakness, and elevated serum creatine kinase. Diagnosis is confirmed by genetic testing and clinical history.

Management focuses on avoiding triggers, maintaining hydration, and supportive treatment during acute episodes; there is no disease-modifying cure. Research continues to define lipin-1’s tissue-specific roles and its contribution to metabolic diseases such as obesity and insulin resistance, with animal models showing essential functions in adipose tissue development and lipid homeostasis.