LYPLAL1, known as lysophospholipase-like 1, is an enzyme with emerging roles in various biological processes. It has been associated with metabolic traits, and a multitude of association studies have shown links between its gene locus variants and conditions such as obesity and insulin resistance. It may be involved in hepatic glucose metabolism, potentially negatively regulating gluconeogenesis and upregulating glycolysis [3].

Knockout of murine Lyplal1 has revealed sex-specific effects. Female Lyplal1 KO mice fed a high-fat, high-sucrose (HFHS) diet weighed less, had reduced body fat percentage, and decreased adipocyte diameter compared to wild-type mice, while male KO mice did not show these differences. Both sexes had reduced liver triglycerides and steatosis [2]. In addition, inhibition of LYPLAL1 significantly enhances cGAS-mediated innate immune response, elevates PD-L1 expression, and enhances anti-tumor response to PD-1 blockade, as LYPLAL1 depalmitoylates cGAS to compromise its normal function [1].

In conclusion, Lyplal1 has sex-specific effects on adiposity and is involved in regulating hepatic glucose metabolism. The Lyplal1 KO mouse model has provided insights into its role in diet-induced obesity and anti-tumor immunity, highlighting its importance in understanding metabolic and immune-related disease mechanisms.