Patatin-like phospholipase domain-containing protein 5 (PNPLA5)

Patatin-like phospholipase domain-containing protein 5 (PNPLA5) is an intracellular serine hydrolase enzyme in the PNPLA family, possessing triacylglycerol lipase activity and characterized by a patatin-like domain that contains a catalytic dyad (serine-aspartic acid) within its N-terminal. PNPLA5 is widely expressed in human tissues, with the highest levels in the brain and pituitary gland. It localizes to cytoplasmic lipid droplets and is upregulated during adipocyte differentiation. Functionally, PNPLA5 regulates intracellular lipid metabolism, particularly triglyceride hydrolysis, and is essential for autophagy initiation by facilitating autophagosome membrane formation. Animal knockout models indicate that PNPLA5 plays critical roles in testicular function (preventing apoptosis), wound healing, inflammation, coagulation, and systemic lipid homeostasis. Disruption of PNPLA5 results in increased triglyceride and cholesterol levels, coagulopathy, and reproductive defects. Currently, PNPLA5 is not targeted by any approved drugs, but its enzymatic activity and involvement in key metabolic and cell survival pathways position it as a potential future therapeutic target for metabolic diseases and conditions involving lipid dysregulation, infertility, or bleeding disorders.

Other names

Patatin-like phospholipase domain-containing protein 5PNPLA5GS2LdJ388M5.4GS2-like proteinpatatin like phospholipase domain containing 5

Not established for drugs (no known drugs directly targeting PNPLA5). Functionally, the protein mediates triacylglycerol hydrolysis, affects lipid droplet homeostasis, and participates in forming membranes during autophagy.