Palmitoyl-protein thioesterase 1 (PPT1) (PPT1)

Palmitoyl-protein thioesterase 1 (PPT1) is a lysosomal enzyme responsible for removing long-chain fatty acids, such as palmitate, from cysteine residues in proteins during degradation. This process, known as depalmitoylation, is crucial for protein turnover and recycling, particularly in neurons where synaptic vesicle proteins are heavily palmitoylated (UniProt P50897). Mutations in the CLN1 gene lead to a deficiency in PPT1 activity, resulting in the accumulation of palmitoylated proteins as granular osmiophilic deposits (GRODs) within lysosomes (NCBI Gene ID: 1201). This accumulation triggers progressive neurodegeneration, characterized by vision loss, motor decline, seizures, and cognitive impairment, typically presenting in infancy as Infantile Neuronal Ceroid Lipofuscinosis (INCL). Therapeutic strategies currently focus on restoring enzyme function through gene therapy, such as AAV-mediated delivery, or enzyme replacement therapy, as well as exploring small molecules that can bypass the enzyme's function to cleave thioester bonds (PubMed: 31553478).

Other names

CLN1Palmitoyl-protein hydrolase 1Ceroid-lipofuscinosis neuronal protein 1PPT

Enzyme replacement therapy (restoring catalytic activity), Gene addition therapy (delivering functional CLN1 gene via viral vector), Small molecule depalmitoylation (non-enzymatic cleavage of thioester bonds)