PPFIA3 encodes a scaffold protein belonging to the LAR protein-tyrosine phosphatase-interacting protein (liprin) family that plays crucial roles in synaptic function and development 1. The protein is involved in synapse formation, synaptic vesicle transport, and presynaptic active zone assembly, with evolutionarily conserved structure and function 12. PPFIA3 functions as a kinesin-cargo linker and may regulate focal adhesion disassembly while localizing receptor-like tyrosine phosphatases at specific plasma membrane sites 3. Disease relevance has emerged through identification of rare heterozygous variants causing a syndromic neurodevelopmental disorder characterized by developmental delay, intellectual disability, hypotonia, autism, and epilepsy 14. Functional studies in Drosophila demonstrate that pathogenic variants act as dominant-negative loss-of-function alleles, with variants in the N-terminal coiled-coil domain showing stronger phenotypic effects than C-terminal variants 12. The variants disrupt multiple developmental processes and synapse formation, leading to seizure-like behaviors, motor defects, and synaptic abnormalities 2. PPFIA3 has also been identified as a novel gene associated with developmental and epileptic encephalopathy with spike-wave activation in sleep, expanding its clinical significance in pediatric neurology 4.