TMEM86A, also known as transmembrane protein 86A, is a putative lysoplasmalogenase. It plays a crucial role in regulating plasmalogen homeostasis, which is associated with various biological processes. Dysregulation of adipose tissue plasmalogen metabolism related to this gene is linked to obesity-related metabolic diseases. Genetic models, like gene-knockout models, are valuable for studying its function [1,2,3].

In adipocyte-specific TMEM86A-knockout (AKO) mice, lysoplasmalogen content in adipose tissue increases, including plasmenyl lysophosphatidylethanolamine 18:0 (LPE P-18:0). This AKO also leads to an increase in protein kinase A signalling pathways due to phosphodiesterase 3B inhibition and cyclic adenosine monophosphate elevation. As a result, mitochondrial oxidative metabolism is upregulated, energy expenditure is elevated, and mice are protected from high-fat-induced metabolic dysfunction [1]. In macrophages, overexpression of Tmem86a reduces lysoplasmalogen abundance and membrane fluidity, while its silencing increases basal lysoplasmalogen levels and abrogates the liver X receptor (LXR)-dependent reduction of this lipid species, indicating its role in sterol-dependent membrane remodeling [2].

In conclusion, TMEM86A is essential for maintaining plasmalogen homeostasis. Through studies using KO mouse models, it has been revealed that TMEM86A plays a significant role in obesity-related metabolic diseases and macrophage membrane remodeling. These findings provide potential therapeutic directions for preventing or treating obesity-related metabolic disorders [1,2].