Lag1

Lag1, also written LAG1, is a gene originally identified in the budding yeast Saccharomyces cerevisiae. The name longevity assurance gene 1 reflects its historical association with lifespan studies, but its well-characterized role is in sphingolipid metabolism. Lag1p encodes a membrane-associated protein that forms part of the ceramide synthase complex with Lac1p. This enzyme catalyzes the acylation of sphingoid bases with fatty acyl-CoA to produce ceramide, a central component of complex sphingolipids. The Lag1–Lac1 complex localizes to the endoplasmic reticulum and determines the acyl-chain composition of ceramides, influencing membrane properties and signaling.

In Saccharomyces cerevisiae, LAG1 and LAC1 are paralogs with overlapping functions. Deletion of either gene alters ceramide synthesis and sphingolipid metabolism, while double mutants exhibit more pronounced defects in growth and stress responses due to disrupted ceramide production. The gene family has conserved homologs in other eukaryotes, including humans, where Lag1-like proteins form part of the LASS (longevity assurance) family of ceramide synthases (also known as CERS1–CERS6). These human enzymes determine ceramide acyl-chain lengths and participate in signaling pathways related to apoptosis, differentiation, and disease.

Overall, Lag1 denotes a key component of ceramide biosynthesis in yeast, with broader relevance to sphingolipid metabolism across species and a historical linkage to aging research through its original naming.