Synaptojanin-1 (SYNJ1)

Synaptojanin-1 is a dual-domain phosphoinositide phosphatase encoded by the *SYNJ1* gene on chromosome 21q22.2[4][5]. It contains an N-terminal SAC1-like domain and a central 5-phosphatase domain, both of which contribute to lipid homeostasis in neurons and other tissues[2][4]. The enzyme hydrolyzes specific phosphate groups from phosphoinositide lipids (notably PI(4,5)P2 and PI(3,4,5)P3), thereby regulating key steps in synaptic vesicle endocytosis and recycling, as well as membrane trafficking and autophagy[1][2][4][5]. The 145 kDa isoform is brain-enriched and has a critical role in clathrin-mediated endocytosis at neuronal synapses, while the 170 kDa isoform is more broadly expressed[2][4]. Mutations and altered expression in Synaptojanin-1 are implicated in a spectrum of human disorders, most notably early-onset Parkinson’s disease, epilepsy, and Down syndrome, highlighting its importance as a potential, yet currently untargeted, therapeutic protein[1][3][4][5].

Other names

Synaptojanin 1SYNJ1KIAA0910INPP5GPARK20Synaptic inositol 1,4,5-trisphosphate 5-phosphatase 1phosphoinositide 5-phosphataseinositol polyphosphate-5-phosphatase Ginositol 5'-phosphatase (synaptojanin 1)DEE53EIEE53

Inhibition of phosphoinositide 5-phosphatase activity Modulation of phosphatidylinositol signaling at synaptic membranes