Plin2, also known as perilipin-2, is a key lipid droplet (LD)-associated protein. It plays an essential role in governing LD metabolism, with implications in pathways related to lipid hydrolysis, autophagy, and epigenetic regulation. Genetic models, such as gene-knockout models, have been crucial in studying its functions [1-5].

In mice, hepatocyte-specific Setdb1-knockout led to increased Plin2 mRNA expression and protein stability, promoting lipid accumulation and hepatosteatosis, suggesting Plin2's role in alcoholic liver disease progression [1]. In embryonic stem cells, Plin2-mediated lipid hydrolysis is critical for pluripotency. Plin2 knockout enhanced lipid hydrolysis, accelerating exit from pluripotency through lipidomic remodeling and histone acetylation changes [2]. In the liver, plin2-/-mice had a 60% reduction in triglyceride (TG) content, enhanced autophagy, and protection against fatty liver disease, indicating Plin2's role in regulating autophagy and hepatic TG levels [3].

In conclusion, Plin2 is vital for lipid droplet metabolism, autophagy regulation, and cell fate determination in processes like pluripotency exit. Mouse knockout models have revealed its significance in diseases such as alcoholic liver disease and fatty liver disease, providing insights into potential therapeutic targets for these conditions.