PLA2G2F encodes a secreted, calcium-dependent phospholipase A2 that hydrolyzes phospholipids at the sn-2 position, with preference for phosphatidylglycerols and phosphatidylethanolamines. The enzyme is primarily expressed in the suprabasal epidermis and regulates skin homeostasis by generating bioactive lipid mediators including ethanolamine lysoplasmalogen and protectin D1 1. PLA2G2F plays a central role in epidermal pathophysiology: knockout mice showed fragile stratum corneum but were protected from psoriasis, contact dermatitis, and skin cancer, while overexpression induced psoriasis-like hyperplasia 1. The enzyme functions within a shared phospholipase A2 pathogenic pathway in psoriasis and pityriasis rubra pilaris by mobilizing phospholipid-eicosanoid pools that promote keratinocyte immune responses 2. Recent work demonstrates that ethanolamine-type lysoplasmalogen produced by PLA2G2F is elevated in psoriasis patients and drives disease pathology; pharmacological removal of this lipid biomarker via lysophospholipase D application attenuated inflammation in mouse models 3. Beyond skin, PLA2G2F expression is regulated in intestinal and neural contexts and associates with lipid metabolism and immune regulation. These findings identify PLA2G2F as a novel therapeutic target for epidermal-hyperplastic diseases, particularly psoriasis, potentially through lipid-directed interventions.