Plin2, also known as perilipin-2, is a key lipid droplet-associated protein. It plays a crucial role in governing lipid droplet (LD) metabolism, with its functions including maintaining lipid droplet stability and inhibiting lipase degradation. It is involved in pathways related to lipid metabolism, autophagy, and is ubiquitously expressed [1,2]. Genetic models, especially knockout models, have been instrumental in studying its functions.

In plin2-/-mice, there is an ∼60% reduction in triglyceride (TG) content, and they are protected against fatty liver disease. PLIN2 deficiency enhances autophagy and depletes hepatic TG, protecting against severe ER stress-induced hepatosteatosis and hepatocyte apoptosis [2]. In embryonic stem cells, Plin2-mediated moderate lipid hydrolysis is critical for pluripotency. Plin2 knockout promotes pluripotency exit through lipidomic remodeling and histone acetylation [3]. In non-small cell lung cancer, Plin2 promoted cellular proliferation and inhibited autophagy by activating the AKT/mTOR pathway [4]. In hepatocellular carcinoma, PLIN2 was frequently upregulated, and its overexpression promoted cell proliferation by inhibiting the degradation of HIF1α [5].

In conclusion, Plin2 is essential for lipid droplet metabolism and stability. Gene knockout models of Plin2 have revealed its role in diseases such as fatty liver disease, and in processes related to cell fate determination like pluripotency exit. In cancer, it is involved in promoting cell proliferation and inhibiting autophagy, suggesting its potential as a prognostic biomarker and therapeutic target in cancer, especially in respiratory and digestive malignancies [6].