Comparative Structural and Functional Analysis of Perilipin-2 (PLIN2) in Dog and Human revealing Extensive Evolutionary Conservation of Lipid Droplet-associated Features

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Perilipin-2 (PLIN2) is a ubiquitously expressed lipid droplet-associated protein that plays a central role in lipid storage, lipid droplet stabilization and cellular lipid metabolism. Although PLIN2 has been extensively investigated in human metabolic disorders and cancer, comparative information regarding its structural conservation across mammalian species remains limited. In the present study, we performed a comprehensive comparative analysis of canine and human PLIN2 using genomic, sequence, structural and physicochemical approaches. Gene organization, transcript variants and protein sequences were curated from public databases, while predicted threedimensional structures were obtained from the AlphaFold protein structure database. multiple sequence alignment, evolutionary conservation analysis, secondary structure prediction, physicochemical characterization and structural quality assessment were performed using established bioinformatics tools. Comparative analysis demonstrated that canine PLIN2 shares approximately 85% amino acid sequence identity with the human ortholog with extensive conservation of residues associated with lipid droplet function. Although both proteins exhibited highly similar amino acid composition and physicochemical characteristics, differences were observed in protein stability indices and C-terminal structural organization. Secondary structure comparison revealed approximately 72% structural similarity, with both proteins predominantly composed of α-helical domains. Structural superposition further indicated that despite strong sequence conservation, conformational differences exist between the predicted three-dimensional models, particularly within flexible terminal regions. Quality assessment of the predicted structures confirmed their suitability for comparative structural analysis. Overall, the high degree of evolutionary conservation observed between canine and human PLIN2 supports the use of canine models for investigating lipid droplet biology and lipid metabolism-associated diseases. These findings provide valuable insights into the structural basis of PLIN2 function and establish a comparative framework for future experimental studies exploring the role of PLIN2 in metabolic disorders, liver diseases and cancer.