PPT2 (palmitoyl-protein thioesterase 2) is a lysosomal thioesterase located on chromosome 6.3 that catalyzes hydrolysis of fatty acyl-CoA substrates 1. Unlike its homolog PPT1, PPT2 preferentially hydrolyzes unbranched palmitoyl-CoA rather than S-palmitoylated proteins, due to structural differences in its lipid-binding groove that restrict bulky head group binding 1. PPT2 performs non-redundant roles in lysosomal thioester catabolism 2, and PPT2 deficiency in mice causes neuronal ceroid lipofuscinosis with distinctive neurodegenerative features including spasticity and ataxia by 15 months, alongside visceral manifestations including bone marrow infiltration, splenomegaly, and pancreatic lipofuscin accumulation 3. While PPT2 mutations have not been confirmed in human neuronal ceroid lipofuscinosis patients at defined loci 4, emerging evidence suggests PPT2 has broader clinical significance. Decreased PPT2 expression correlates with poor ovarian cancer prognosis and predicts better immunotherapy response 5. A long noncoding RNA transcript (PPT2-EGFL8) functions as a competing endogenous RNA regulating retinal neovascularization in diabetic retinopathy 6. Additionally, PPT2 was identified as a mitochondrial metabolism-related biomarker downregulated in coronary heart disease 7. These findings suggest PPT2 functions beyond classical lysosomal lipid catabolism in disease pathogenesis.