Early Human Evidence for Increased SPTLC3 Expression in NAFLD/NASH

Non-alcoholic fatty liver disease (NAFLD) and its progressive form, non-alcoholic steatohepatitis (NASH), involve substantial alterations in hepatic lipid and sphingolipid metabolism. While the serine palmitoyltransferase (SPT) complex catalyzes the rate-limiting step of de novo sphingolipid synthesis, research in fatty liver disease has historically centered on the canonical catalytic subunits SPTLC1 and SPTLC2. By contrast, the SPTLC3 isoform has received comparatively limited attention in human liver disease. This Perspective highlights early human evidence for increased SPTLC3 expression in NASH. Notably, a 2013 doctoral thesis provides the earliest explicit description of elevated SPTLC3 expression in human NASH liver tissue, preceding later peer-reviewed studies that examined SPTLC3 expression in NAFLD/NASH. No new experimental data are presented; all observations derive exclusively from previously published and publicly accessible sources.