Lysosomal thioesterase PPT2 (PPT2)

Lysosomal thioesterase PPT2 (PPT2) is a glycosylated lysosomal enzyme classified as a thioesterase and hydrolase that catalyzes the hydrolysis of thioester bonds from unbranched lipid substrates such as S-palmitoyl-CoA[2][3][8]. Unlike its homolog PPT1, PPT2 does not act on palmitoylated proteins or palmitoylcysteine, highlighting distinct substrate specificity and non-redundant biological roles[3][8]. PPT2 is involved in the breakdown of long-chain fatty acids within lysosomes and is implicated in cell metabolism, specifically lipid metabolism[1][2][8]. Experimental manipulations indicate that reduced PPT2 expression promotes epithelial-to-mesenchymal transition and cancer progression (e.g., renal cell carcinoma and ovarian cancer), and its overexpression suppresses tumor cell proliferation and invasion[1][4]. Deficiency in PPT2 in mouse models leads to a form of neurodegeneration resembling neuronal ceroid lipofuscinosis, with unique visceral and neurological symptoms not fully recapitulated by PPT1 deficiency[5][7]. Recent genetic studies also associate PPT2 with pulmonary diseases via its locus, suggesting broader implications in human health[9]. Currently, PPT2 is considered a promising prognostic biomarker in selected cancers, whereas no approved drugs selectively target PPT2 in clinical practice.

Other names

Palmitoyl-protein thioesterase 2PPT2PPT-2S-thioesterase G14C6orf8G14VE-statin2Palmitoyl-protein hydrolase 2

Not well established for existing drugs; potential mechanisms include modulation of lipid metabolism and epithelial-to-mesenchymal transition (EMT) via PPT2 expression in cancer contexts[1][4].