Polyphosphatidylinositol phosphatase SYNJ1

Synaptojanin-1 (SYNJ1) is a phosphatase that catalyzes the dephosphorylation of phosphoinositides, including phosphatidylinositol 4-phosphate, PIP2, and PIP3 (UniProt: O43426). The protein participates in clathrin-mediated endocytosis and regulates actin filament dynamics by hydrolyzing PIP2 bound to actin regulatory proteins, thereby modulating downstream signaling from tyrosine kinases and ASH/GRB2.

SYNJ1 is associated with early-onset Parkinson disease (PARK20) and developmental and epileptic encephalopathy 53 (DEE53), indicating its importance in neuronal function and synaptic homeostasis (UniProt: O43426). These monogenic disease associations highlight the protein's critical role in neurodegeneration and neurodevelopmental pathways.

In Alzheimer's Disease, SYNJ1 shows an ambiguous regulation pattern across subcellular fractions in post-mortem AD brain compared to age-matched controls (Chaparral AD proteomics). The mean log2 fold-change is modest at 0.22, suggesting minimal net change in overall protein abundance, though direction varies by cellular compartment in this TMT-labeled proteomics study.